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Tag: Cancer Center Featured Story 2

  • New Class of Drugs May Prevent Infection by Wide Range of COVID-19 Variants

    New Class of Drugs May Prevent Infection by Wide Range of COVID-19 Variants

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    RESEARCH SUMMARY

    Publication: Nature Genetics https://www.nature.com/articles/s41588-023-01307-z

    Dana-Farber Cancer Institute author: Cigall Kadoch, PhD,

     

    Summary:

    A new class of oral drugs can inhibit a wide range of SARS-CoV-2 variants, researchers report, potentially identifying new antiviral agents providing broad activity against the constantly emerging new strains of the COVID-19 virus. The researchers discovered that the mammalian SWI/SNF (also called BAF) chromatin remodeling complex, a regulator of gene expression –controls the expression of the ACE2, the cellular receptor or “entry point” used by COVID-19 viruses.  When mSWI/SNF complexes were disrupted, the cell could no longer make ACE-2 receptor protein and became resistant to infection by any virus that uses that receptor. Kadoch’s work on mSWI/SNF complexes over the years has led to experimental drugs currently in phase 1 trials as anti-cancer agents. These oral drugs now are looking promising for use in COVID-19, since they can inhibit ACE2 activity and nearly completely block viral infection in multiple cell lines and human lung organoids.

    Impact:

    The formerly potent array of monoclonal antibody treatments for COVID-19 continue to lose their activity as new less-sensitve variants of the virus appear: indeed, one by one, they have gone off the market. The need for more broadly acting agents against new and drug-resistant viruses is great. With the identification of this new target – a druggable chromatin regulatory complex – inhibition of which prevents infection of host cells, Kadoch and co-author Craig Wilen, MD, PhD, of the Yale Cancer Center have found a promising novel approach to combating the constantly-changing SARS virus.

    Funding:

    This work was supported by NIH grants K08AI128043, Burroughs Wellcome Fund, Smith Family Foundation, Ludwig Family Foundation, Huffington Foundation, Mathers Foundation, Emergent Ventures Fast Grant, and NIH Director’s New Innovator Award 1DP2CA195762-01.

     

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    Dana-Farber Cancer Institute

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  • National Comprehensive Cancer Network Announces Collaboration with Blood Cancer Experts in Poland

    National Comprehensive Cancer Network Announces Collaboration with Blood Cancer Experts in Poland

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    Newswise — PLYMOUTH MEETING, PA [February 27, 2023] — Today, the National Comprehensive Cancer Network® (NCCN®)—a not-for-profit alliance of leading United States cancer centers—announced a new collaboration with the Institute of Hematology and Transfusion Medicine in Poland (IHIT), and the Alliance For Innovation—Polish-American Foundation (AFI). The three organizations have signed an agreement enabling clinicians to share their established expertise and international experience in order to improve quality of care and outcomes for patients with hematologic malignancies in Poland and around the world.

    “This new agreement highlights our commitment to continue advancing our ongoing collaboration with Polish colleagues to standardize and improve how cancers are managed,” said Robert W. Carlson, MD, Chief Executive Officer, NCCN. “The Institute of Hematology and Transfusion Medicine in Poland is the leading medical and research hospital in Poland for hematology; it serves as a national clinical and diagnostic reference center. Together, we can make sure more people with blood cancers receive region-appropriate treatment based on the latest evidence and expert consensus.”

    This new agreement builds on a multi-year collaboration between NCCN, the Marie Curie-Sklodowska National Research Institute of Oncology, Republic of Poland Ministry of Health, and AFI to improve country-specific guidelines for solid tumor diagnostic and therapeutic procedures in Poland, based on the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) —as called for in Poland’s National Cancer Strategy. NCCN Guidelines® are the recognized standard for clinical direction and policy in cancer management and the most thorough and frequently-updated clinical practice guidelines available in any area of medicine. They have been translated, adapted, and harmonized in collaboration with local and regional experts, advocates, and policymakers across Sub-Saharan Africa, the Middle East and North Africa (MENA), the Caribbean, Asia, South America, and Europe, in order to make them more relevant and accessible to patients and care providers worldwide. The initial work with Poland launched in 2021; to date, the groups have co-developed Polish NCCN Guidelines Adaptations for:

    • Central Nervous System Cancers,
    • Cervical Cancer,
    • Colon Cancer,
    • Head and Neck Cancers, and
    • Ovarian Cancer

    “Our main goal is to improve the quality of care and outcomes for hematologic patients in Poland,” said Prof. Ewa Lech-Marańda, Director of the IHIT. “The cooperation between our institutions will include the development of adapted clinical guidelines based on NCCN’s knowledge, experience, and expertise, as well as longstanding procedures for continuous updates.”

    “The signing of an agreement between such important cancer control institutions is of great importance for patients and the oncological community, as well as for the further development of Polish-American cooperation,” said Marcin Hańczaruk, Co-Chairman of AFI.

    NCCN’s resources for cancer patients and providers are widely accessed and utilized free-of-charge around the world. Nearly half of the 1.7 million registered users who view NCCN Guidelines at NCCN.org or via the Virtual Library of NCCN Guidelines® app are located outside of the U.S. Learn more about NCCN’s collaborative work to define and advance high-quality, high-value, patient-centered cancer care globally at NCCN.org/global.

    # # #

    About the National Comprehensive Cancer Network

    The National Comprehensive Cancer Network® (NCCN®) is a not-for-profit alliance of leading cancer centers devoted to patient care, research, and education. NCCN is dedicated to improving and facilitating quality, effective, equitable, and accessible cancer care so all patients can live better lives. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) provide transparent, evidence-based, expert consensus recommendations for cancer treatment, prevention, and supportive services; they are the recognized standard for clinical direction and policy in cancer management and the most thorough and frequently-updated clinical practice guidelines available in any area of medicine. The NCCN Guidelines for Patients® provide expert cancer treatment information to inform and empower patients and caregivers, through support from the NCCN Foundation®. NCCN also advances continuing education, global initiatives, policy, and research collaboration and publication in oncology. Visit NCCN.org for more information.

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    National Comprehensive Cancer Network(r) (NCCN(r))

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  • Black patients wait longer for uterine cancer testing, diagnosis

    Black patients wait longer for uterine cancer testing, diagnosis

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    Newswise — Early diagnosis of uterine cancer is known to improve a patient’s chances for survival, but previous research has found that Black patients are less likely to receive early diagnoses than people of other racial and ethnic groups. A new analysis by Yale researchers provides insights into why that is: They found that Black patients were more likely than their white counterparts to experience testing delays or to not receive recommended tests at all.

    The findings were published Feb. 15 in the Journal of the National Cancer Institute.

    At what stage a patient is diagnosed with uterine cancer has a major impact on how well that patient will fare. When diagnosed while the cancer is still confined to the uterus, nearly 95% of patients will survive the next five years. But that rate drops to less than 70% once the cancer has spread to areas or lymph nodes nearby and plummets to around 18% once the cancer has spread to other parts of the body.

    “Early diagnosis is important,” said Xiao Xu, an associate professor of obstetrics, gynecology, and reproductive sciences at Yale School of Medicine, member of Yale Cancer Center, and lead author of the study. “We don’t know why there’s a racial disparity in early diagnosis and until we do, it’s hard to address it.”

    To determine whether differences in the diagnosis process contribute to this disparity, Xu and her colleagues used the MarketScan Multi-State Medicaid Database, which has deidentified data from more than 44 million Medicaid patients across the United States.

    For their analysis, they included adult patients who had reported abnormal uterine bleeding to their health care providers and later received a diagnosis of uterine cancer. Abnormal uterine bleeding is the most common symptom of uterine cancer, Xu said, and can present as light spotting or heavier bleeding at unexpected times.

    The American College of Obstetricians and Gynecologists recommends several procedures to evaluate the cause of abnormal uterine bleeding, such as endometrial biopsy, transvaginal/pelvic ultrasound, and hysteroscopy, in which a physician examines the inside of the cervix and uterus with a small, telescope-like device. In the new study, researchers found that more than twice as many Black patients than white patients did not receive any of these procedures (10.1% of Black patients versus 5% of white patients).

    Further, of the patients who did receive procedures, Black patients were more likely than white patients to experience a delay of more than two months in receiving their first diagnostic procedure following their report of abnormal uterine bleeding.

    Ultimately, Black patients were more likely than white patients to experience a delay in receiving their cancer diagnosis. The researchers found that 11.3% of Black patients who’d reported abnormal uterine bleeding waited more than a year to receive a uterine cancer diagnosis, compared with 8.3% of white patients.

    “Overall, we found a pretty consistent difference in the quality of care received by Black and white patients,” said Xu.

    To better understand the driving factors behind this difference in care and how best to address them, Xu and her colleagues are evaluating additional sets of data to determine whether Black patients might experience barriers to accessing specialist care, if more education about the symptoms of uterine cancer may be beneficial for patients, and whether delays in diagnoses result in patients being diagnosed at later stages of cancer. They are also studying whether these findings among Medicaid patients are similarly seen in other patient populations.

    “The goal,” said Xu, “is for every patient to receive high-quality care.”

    Other authors include Marcella Nunez-Smith and Mitchell Clark from Yale School of Medicine and Ling Chen and Jason Wright from Columbia University.

    The research was supported by the National Institute on Minority Health and Health Disparities.

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    Yale Cancer Center

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  • $3 million national grant to fund pancreatic cancer study

    $3 million national grant to fund pancreatic cancer study

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    Newswise — UC Davis Comprehensive Cancer Center is partnering with TargaGenix and Northeastern University to study pancreatic ductal adenocarcinoma (PDAC). The often-lethal cancer has an average five-year survival rate of less than 11%. The academic-industry partnership will receive nearly $3 million over five years thanks to National Institutes of Health (NIH) funding through its R01 grant program. The NIH gives R01 grants only to mature research projects driven by strong preliminary data.

    The team will develop a treatment based on the novel chemotherapy TGX-1214, in combination with cancer immunotherapy. The researchers expect that by the end of the study, this will become part of a new treatment option for PDAC patients.

    PDAC accounts for more than 90% of pancreatic cancer cases. It is usually diagnosed at a late stage when disease has spread to other organs. Symptoms are often common and non-specific, such as lack of appetite and weight loss. By the time symptoms appear, the disease is at a late stage, making it inoperable and incurable.

    Current challenges treating pancreatic cancer

    “Surgery, which offers the only realistic hope for a cure, is a viable option in only a limited number of patients, and current chemotherapy and radiation therapy offer limited or no benefit at all,” UC Davis pancreatic cancer researcher Gerardo Mackenzie said.

    Mackenzie is an associate professor in the Department of Nutrition. He and UC Davis oncologist and Medical Director of the cancer center’s Office of Clinical Research Edward J. Kim are the UC Davis principal investigators for the study.

    “The current chemotherapy combinations used to treat PDAC have marginally improved survival outcomes. The average survival in advanced disease is still less than a year. The limited benefit of these therapies, unfortunately, comes at the cost of significant toxicities, including suppressed immune system, fatigue, nausea, diarrhea, and nerve damage, limiting their use to patients with relatively preserved function,” Kim said, “And most patients still ultimately relapse and progress.”

    In addition, studies show that new immuno-oncology agents, such as anti-PD-1 or anti-CTLA-4 are not effective in PDAC. This is partly because the drugs create a microenvironment that weakens the immune system and prevent cancer-fighting T-cells from entering the tumor mass.

    “That’s why there is a critical unmet need to develop better therapeutic options for aggressive and refractory PDAC,” said distinguished professor of pharmaceutical sciences and chemical engineering at Northeastern University. Amiji is Northeastern’s principal investigator for the study and the scientific advisor for TargaGenix. “We are pleased to collaborate with colleagues at UC Davis and TargaGenix on this research. Based on the high mortality associated with pancreatic cancer, the opportunity for us to develop TGX-1214 for this dreadful disease is especially exciting.”

    Promising TGX-1214 combination strategy for the treatment of advanced pancreatic cancer

    The team will leverage the multi-disciplinary expertise of scientists and clinicians to develop an effective treatment based on the combination of TGX-1214 and immune checkpoint inhibition, which block proteins called checkpoints. Immune checkpoint inhibitors help T cells kill cancer cells better.

    Previous studies indicate that TGX-1214 is safe and effective in multiple animal studies. In preliminary studies, TGX-1214 strongly inhibited pancreatic cancer growth, with complete tumor regression in two pre-clinical models of pancreatic cancer.

    The long-term goal of the research is to develop safe and effective treatment strategies for PDAC to test in clinical trials that will become available for patients.

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    UC Davis Comprehensive Cancer Center

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  • Targeted therapy momelotinib provides significant symptom and anemia improvements in patients with myelofibrosis

    Targeted therapy momelotinib provides significant symptom and anemia improvements in patients with myelofibrosis

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    Newswise — Patients with myelofibrosis had clinically significant improvement in disease-related symptoms, including anemia and spleen enlargement, when treated with the targeted therapy momelotinib, according to results from the international Phase III MOMENTUM trial led by researchers at The University of Texas MD Anderson Cancer Center.

    The findings, published today in The Lancet, support the use of momelotinib – a potent ACVR1/ALK2 and JAK1/2 inhibitor – over the standard therapy danazol in treating myelofibrosis patients that were resistant, refractory or intolerant to firstline therapy, especially symptomatic patients and those with anemia.

    “Current options for managing anemia in our myelofibrosis patients provide only modest and temporary benefits, so we are excited about these findings,” said study lead Srdan Verstovsek, M.D., Ph.D., professor of Leukemia. “The trial results suggest that momelotinib is safe, well-tolerated and can improve one of the most common and debilitating clinical problems for this patient population.”

    Myelofibrosis is an uncommon bone marrow cancer that is part of a group of diseases known as myeloproliferative neoplasms. A hallmark of the disease is dysregulated JAK signaling, which disrupts the body’s normal production of blood cells and leads to common symptoms, including an enlarged spleen and anemia. Chronic anemia in these patients is associated with poor prognoses.

    Currently approved JAK inhibitors can improve spleen responses and other disease-related symptoms, but they also can worsen anemia. In this trial, momelotinib improved anemia and reduced transfusion dependency in myelofibrosis patients previously treated with a JAK inhibitor. Momelotinib can be administered and maintained at full dose because it does not suppress bone marrow activity like other JAK inhibitors.  

    The MOMENTUM trial is the first randomized Phase III study to evaluate a JAK1/2 and ACVR1/ALK2 inhibitor in patients with myelofibrosis and anemia. The trial was designed to compare the clinical benefits of momelotinib to danazol, a synthetic androgen currently used to treat anemia in symptomatic myelofibrosis patients.

    The study enrolled 195 adult patients from 107 research sites across 21 countries. Trial participants were randomly assigned (2:1) to receive momelotinib plus placebo or danazol plus placebo. Sixty-three percent of participants were male and 37% were female. The median age of participants for the momelotinib group was 71 years and for the danazol group 72 years.

    The trial’s primary endpoint was symptom reduction after 24 weeks of treatment, defined as a 50% or more reduction in Myelofibrosis Symptom Assessment Form Total Symptom Score. A significantly greater proportion of patients who received momelotinib saw benefits in their disease symptoms (25%) compared to those receiving danazol (9%).

    Patients treated with momelotinib also experienced a significant reduction in their spleen size, with 25% responding after 24 weeks of therapy. Additionally, these patients required fewer blood transfusions compared to those receiving danazol.

    The safety profile of momelotinib was comparable to previous clinical trials. The most common non-hematological side effects experienced by trial participants in the momelotinib group included diarrhea, nausea, weakness and itching or irritated skin.

    “If approved, momelotinib could offer an effective option for patients with myelofibrosis to improve anemia, splenomegaly and other disease-related symptoms over other approved medications so far,” Verstovsek said. “Momelotinib may also be an ideal partner for combinations with other investigational agents in development to further control myelofibrosis symptoms.”

    Patient follow-up is ongoing and long-term survival continues to be monitored.

    The research was supported by Sierra Oncology. A full list of collaborating authors and their disclosures can be found with the full paper here.

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    University of Texas M. D. Anderson Cancer Center

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  • Study Links Key Activating Enzymes to Specific Sites on Proteins in Cells

    Study Links Key Activating Enzymes to Specific Sites on Proteins in Cells

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    RESEARCH SUMMARY

    Study Title: An atlas of substrate specificities for the human serine/threonine kinome

    Publication: Nature (Online) January 11, 2023   https://www.nature.com/articles/s41586-022-05575-3

    Dana-Farber Cancer Institute author: Lewis C. Cantley, PhD

    Summary:

    Thousands of proteins in a human cell are regulated by phosphorylation — the addition of small chemical groups to the proteins’ amino acids by enzymes called protein kinases. This process is known as phosphorylation. Abnormal protein phosphorylation has been implicated in a number of diseases, notably cancer and degenerative diseases like Parkinson’s and Alzheimer’s. Some 90,000 sites of phosphorylation on serine and threonine amino acids have been identified, but it hasn’t been known which of more than 300 protein serine or threonine kinases are responsible. In a new study, researchers at Weill Cornell Medicine and Dana-Farber Cancer Institute purified and characterized the substrate specificity of essentially all the human protein-serine/threonine kinases and developed a computational method to identify the kinases capable of phosphorylating every known phosphorylation site in the human serine/threonine proteome.

    Impact:

    Several thousand sites of serine and threonine phosphorylation have been associated with human diseases, including cancers and diabetes. The new study provides a mechanism for rapidly identifying the protein kinase that is driving the abnormal behavior of individual cancers.  Since many drugs for inhibiting protein kinases are already approved or in clinical trials, this information can rapidly lead to a new therapy that can be individualized to the patient.

    Funding:

    The research was supported by the Leukemia & Lymphoma Society and grants from the National Institutes of Health; the Cancer Research UK and Brain Tumor Charity; the Charles and Marjorie Holloway Foundation, and the MIT Center for Precision Cancer Medicine.

     

     

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    Dana-Farber Cancer Institute

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  • AACI Welcomes LSU-LCMC Health Cancer Center

    AACI Welcomes LSU-LCMC Health Cancer Center

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    Newswise — This month Louisiana State University-Louisiana Children’s Medical Center (LSU-LCMC) Health Cancer Center became the 108th member of the Association of American Cancer Institutes (AACI).

    The LSU-LCMC Health Cancer Center was established in 2021, when LCMC Health announced its commitment of $75 million to LSU over the next five years. The investment will support LSU’s journey to NCI designation through enhanced cancer research and treatment STEM education programs for future health care professionals. Professor of Surgery and Interdisciplinary Oncology John H. Stewart, IV, MD, MBA, is the founding director of the cancer center.

    Under Dr. Stewart’s leadership, the cancer center aims to reduce the cancer burden of Louisiana—particularly in New Orleans and surrounding parishes—through novel discoveries; improved access to advanced cancer treatments and clinical trials; community outreach and engagement; and training and education. Initiatives will integrate disease-specific research and care delivery with a patient-oriented approach that reflects the unique needs of the center’s catchment area.

    LSU-LCMC Health Cancer Center places a special emphasis on head and neck, breast, and prostate cancer screenings, and offers an active AIDS-related malignancies program that employs focused anal and cervical cancer screenings for high-risk populations.

    “We are pleased to welcome LSU-LCMC Health Cancer Center as AACI’s first new member of 2023,” said AACI Executive Director Jennifer W. Pegher. “The cancer center’s commitment to serving a diverse catchment area and training the next generation of oncology professionals aligns with AACI’s values.”

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    AACI’s mission is to accelerate progress against cancer by enhancing the impact of North America’s leading academic cancer centers. For more information, please visit aaci-cancer.org.

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    Association of American Cancer Institutes (AACI)

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  • Study discovers triple immunotherapy combination as possible treatment for pancreatic cancer

    Study discovers triple immunotherapy combination as possible treatment for pancreatic cancer

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    Newswise — HOUSTON ― Researchers at The University of Texas MD Anderson Cancer Center have discovered a novel immunotherapy combination, targeting checkpoints in both T cells and myeloid suppressor cells, that successfully reprogrammed the tumor immune microenvironment (TIME) and significantly improved anti-tumor responses in preclinical models of pancreatic cancer.

    In this study, published today in Nature Cancer, researchers used comprehensive immune profiling in mouse and human pancreatic cancers to systematically identify mechanisms of immunotherapy resistance and investigate potential therapeutic targets. They found that neutralizing several distinct immunosuppressive mechanisms of the TIME dramatically improved survival rates in laboratory models, pointing to a potential treatment option for this notoriously lethal and unresponsive cancer.  

    “This triple combination therapy led to an unprecedented curative response in our models,” said corresponding author Ronald DePinho, M.D., professor of Cancer Biology. “The prevailing view has been that pancreatic cancer is impervious to immunotherapy, but this preclinical study shows that it can be vulnerable to the right combination therapy. Moreover, the presence of these targets in human pancreatic cancer specimens raises the exciting possibility that such therapeutic combinations could one day help our patients.”

    Pancreatic cancer is one of the leading causes of cancer death in the United States, partially because 80% of cases are diagnosed at an advanced stage. Pancreatic cancer is also considered to be “non-immunogenic,” meaning it is unresponsive to commonly used anti-PD-1 and anti-CTLA-4 immune checkpoint inhibitors. This is due in part to the immunosuppressive conditions in the TIME, but the mechanisms behind this resistance are not fully understood.

    The researchers used high-dimensional immune profiling and single-cell RNA sequencing to study how the TIME is affected by a variety of immunotherapies. They identified specific immune checkpoint proteins, 41BB and LAG, that were highly expressed in exhausted T cells.

    In testing antibodies targeting these checkpoints, the researchers observed that models treated with a 41BB agonist and LAG3 antagonist in combination had slower tumor progression, higher levels of anti-tumor immunity indicators and significantly improved survival rates compared to treatment with either antibody alone or with other checkpoint inhibitors. Notably, these preclinical studies faithfully mirrored the human data in their lack of efficacy of anti-PD1 or anti-CTLA-4 therapy.

    The researchers also confirmed these two therapeutic targets are present in human pancreatic cancer samples, with 81% and 93% of patients analyzed having T cells with 41BB and LAG3 expression, respectively. 

    Because this dual-therapy combination did not completely eliminate established tumors, the investigators also examined efforts to reprogram the TIME to further sensitize tumors to immunotherapy. At baseline, the TIME contained an abundance of myeloid-derived suppressor cells (MDSCs) expressing CXCR2, a protein associated with recruiting immunosuppressive cells. Inhibiting CXCR2 alone decreased MDSC migration and blocked tumor growth, but it was not curative. This prompted the investigators to consider a combination targeting 41BB, LAG3 and CXCR2.

    It was this triple combination that resulted in complete tumor regression and improved overall survival in 90% of preclinical models. In a more stringent lab model that develops multiple spontaneously arising tumors with higher treatment resistance, the combination achieved complete tumor regression in over 20% of cases.

    “These are encouraging results, especially considering the lack of effective immunotherapy options in pancreatic cancer,” DePinho said. “By targeting multiple synergistic mechanisms that get in the way of the immune response, we can give T cells a fighting chance to attack these tumors. Of course, we still need to see how this combination translates into a safe and effective regimen in the clinic, and we invite other researchers to build upon these results. We are optimistic that pancreatic cancers, and hopefully other non-immunogenic cancers, can ultimately be rendered vulnerable to combination immunotherapy.”

    The authors point out that these particular immunotherapy agents currently are undergoing clinical trials as monotherapies, suggesting potential opportunities to rapidly translate this triple combination into clinical studies.

    This work was supported by the National Institutes of Health/National Cancer Institute (P01 CA117969, RO1CA240526, RO1CA236864, R01CA231349, R01CA220236, P50CA221707),  the Elsa U. Pardee Foundation, MD Anderson’s Advanced Scholar Program, the Eleanor Russo Fund for Pancreatic Research, Ralph A. Loveys Family Charitable Foundation, the Cultural & Charitable Club of Somerset Run, the New Jersey Health Foundation, the Sheikh Ahmed Bin Zayed Al Nahyan Center for Pancreatic Cancer Research, and MD Anderson’s Pancreatic Cancer Moon Shot®. A full list of collaborating authors and their disclosures can be found with the full paper here.

     

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    University of Texas M. D. Anderson Cancer Center

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  • Ellis Fischel Cancer Center Becomes AACI’s Newest Member

    Ellis Fischel Cancer Center Becomes AACI’s Newest Member

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    Newswise — The Association of American Cancer Institutes (AACI) is pleased to add Ellis Fischel Cancer Center, a part of University of Missouri (MU) Health Care, to its membership roster.

    The Ellis Fischel State Cancer Hospital opened in 1940 as an 85-bed facility equipped with the latest technology of the time for combating cancer. It was the first cancer center west of the Mississippi River, the second in the country, and a trailblazer in establishing multidisciplinary cancer care.

    Today, Ellis Fischel Cancer Center provides cancer care, conducts groundbreaking research, and offers high-quality education, training, and community outreach programs.

    The center is directed by Gerhard Hildebrandt, MD, chief of hematology/oncology and Nellie B. Smith Endowed Chair of Oncology at the MU School of Medicine. With more than 200 cancer- focused researchers across four Missouri campuses, the center has launched an innovative plan to create a consortium partnership with another AACI member, Siteman Cancer Center.

    “We are delighted to welcome the Ellis Fischel Cancer Center as AACI’s fourth new member of 2022 and 107th overall,” said AACI Executive Director Jennifer W. Pegher. “The institute’s commitment to outstanding cancer care, groundbreaking research, and high-quality education, training, and community outreach programs is a catalyst for accelerating progress against cancer.”

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    AACI’s mission is to accelerate progress against cancer by enhancing the impact of North America’s leading academic cancer centers. For more information, please visit aaci-cancer.org.

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    Association of American Cancer Institutes (AACI)

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  • Comparing the cost-effectiveness of treatments for blood clots in cancer patients

    Comparing the cost-effectiveness of treatments for blood clots in cancer patients

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    Newswise — Research conducted by UC Davis Comprehensive Cancer Center and the University of Cincinnati shows that direct oral anti-coagulant (DOAC) drugs are more effective and are more cost-effective than low molecular weight heparin (LMWH) for treating cancer-associated thrombosis (CAT).

    A new study to be published in the Annals of Internal Medicine on December 27, 2022, examines the cost-effectiveness of the four most utilized anticoagulation strategies for blood clots, which include LMWH, apixaban, edoxaban and rivaroxaban. Authors of the study include oncologist and Assistant Professor of Medicine Shuchi Gulati, a clinician scientist with UC Davis, and Professor Emeritus of Clinical Medicine Mark H. Eckman with the University of Cincinnati.

    “For reasons not completely understood, cancer can increase the risk of blood clots, and treatments such as chemotherapy can further increase the risk. Cancer patients with CAT face double the mortality rate compared to cancer patients without thrombosis. CAT also adds a significant financial burden for these patients,” said Gulati who is the corresponding author for the study.

    For many years, injection of low molecular weight heparin has been the treatment of choice in patients who have cancer-associated thrombosis. The DOACs came on the scene about eight or nine years ago, and they have better safety and efficacy profiles.

    “Clinical trials have shown improved efficacy and a decreased risk of major bleeding with the DOACs, but the question is whether people will be willing to pay the additional cost to get the better outcome. Many oncologists have already adopted DOACs in their clinical practice, so this is a key issue,” Gulati said.

    These drugs were compared head-to-head using a computer model Eckman and Gulati constructed that simulates major health events that happen to a cohort of patients with cancer over time who have experienced a blood clot. The model simulates events including recurrent pulmonary emboli, recurring DVT without pulmonary emboli, major bleeds and clinically relevant non-major bleeds as well as mortality. Then, over the course of the lifetime of the patient cohort, the study examined the accumulating lifetime costs and lifetime effectiveness measured in a metric called quality-adjusted life years (QALYs).

    “QALYs are basically years lived by the members of the cohort but adjusted for the quality of life in the different health states they experience over that time,” Gulati said. “If you were to have a recurrent blood clot or a major bleed for instance, you would have a decrease in your quality of life.”

    In the base-case analysis, using the cost of drugs purchased at a federal facility such as the Veteran’s Administration, apixaban was favored as being more effective and less costly than either LMWH or edoxaban while indicating rivaroxaban was not cost-effective. However, the study results were vastly different when analyzing average prices from GoodRx, a free online service that provides drug coupons for discounts on medications. In this scenario, if decision makers were unwilling to spend more than $50,000 per QALY, edoxaban was favored, and using the contemporary threshold for societal willingness to pay, rivaroxaban was cost-effective, with an incremental cost-effectiveness ratio of just more than $50,000 per QALY.

    Gulati said the findings demonstrate a stark difference between the real-world cost of direct oral anticoagulants and drug prices from the Veteran’s Administration and will likely have implications for value-based price benchmarks in the United States. She added that an individual’s insurance coverage plan can make a huge difference in the patient’s out-of-pocket costs for these medications.

    “Most importantly, all the DOACs are more effective and have a better side-effect profile than low molecular weight heparin,” Eckman concluded. “Which of those is the most cost-effective is going to depend for any given patient on what the cost of those drugs will be for them. That decision can be one that is made in concert with the oncologist and the patient.”

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    UC Davis Comprehensive Cancer Center

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  • Sotorasib shows clinically meaningful activity in KRAS G12C-mutated advanced pancreatic cancer

    Sotorasib shows clinically meaningful activity in KRAS G12C-mutated advanced pancreatic cancer

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    Newswise — In the Phase I/II CodeBreaK 100 trial, the KRAS G12C inhibitor sotorasib achieved meaningful anticancer activity with an acceptable safety profile in heavily pretreated patients with KRAS G12C-mutated metastatic pancreatic cancer, according to researchers at The University of Texas MD Anderson Cancer Center.

    The results of the trial, published today in the The New England Journal of Medicine, indicate an objective response rate of 21.1% and a median time-to-response of 1.5 months, with 84% of patients experiencing disease control. Median progression-free survival was 4 months and overall survival was 6.9 months.

    “These are encouraging early data because they point toward establishing that KRAS inhibitors can work in pancreatic cancers, which have been difficult to crack from a targeted therapy standpoint,” said principal investigator David S. Hong, M.D., professor of Investigational Cancer Therapeutics. “We look forward to data from larger trials as we continue working to bring much-needed new therapies to these patients.”

    The KRAS protein is part of a normal signaling pathway regulating growth and proliferation of cells, but activating mutations in KRAS drives abnormal growth in cancer. KRAS mutations are especially common in pancreatic cancers, occurring in about 90% of patients, while KRAS G12C mutations are present in 1-2% of cases.

    Sotorasib is a small-molecule inhibitor that irreversibly binds the mutant KRAS G12C protein to lock it in an inactive state. In 2021, this targeted therapy was approved by the Food and Drug Administration for the treatment of KRAS G12C-mutated metastatic non-small cell lung cancer, based on previous data from another cohort of this study.

    The pancreatic cancer cohort enrolled 38 patients with metastatic disease and a median of two prior lines of therapy. The median age of participants was 65.5, 76.3% were men and 55.3% had stage IV disease at initial diagnosis.

    All patients experienced treatment-emergent adverse events, the most common of which were abdominal pain (36.8%), diarrhea and nausea (23.7% each). Treatment-related adverse events were reported in 42.1% of patients, of which 15.8% were grade 3. The most frequently occurring grade 3 toxicities were diarrhea and fatigue (5.3% each). No adverse events resulted in discontinuation of treatment.

    According to Hong, these results may be a harbinger of success for other drugs in the pipeline targeting mutant KRAS that could potentially benefit far greater numbers of patients.

    “It’s gratifying to see results like this, since targeting mutant KRAS seemed virtually impossible just a few years ago. Still, we must continue our research efforts to make progress against other common KRAS mutations found in pancreatic and other cancer types,” Hong said. “Trials have recently begun on drugs targeting KRAS G12D, a much more common mutation in pancreatic cancer, as well as some pan-RAS therapies, which target multiple mutations.”

    This study was funded by Amgen. The work was also supported in part by the National Institutes of Health (P30 CA008748, P30 CA016672, 1UL1 TR003167), the Cancer Prevention and Research Institute of Texas (RP150535), and the Sheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy at MD Anderson. A full list of authors and their disclosures can be found in the paper here.

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    University of Texas M. D. Anderson Cancer Center

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  • Investigators Develop Model to Predict Overall Survival in Adults Diagnosed with Advanced Stage Hodgkin Lymphoma

    Investigators Develop Model to Predict Overall Survival in Adults Diagnosed with Advanced Stage Hodgkin Lymphoma

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    ********** UNDER EMBARGO UNTIL Saturday, December 10 at 5:10 PM EST (4:10 PM CST) ***********

    Newswise — New Brunswick, NJ and Boston, MA, December 10, 2022 – Investigators from Rutgers Cancer Institute of New Jersey, the state’s only NCI-designated Comprehensive Cancer Center and leading cancer program along with Tufts Medical Center in Boston, developed  and validated the Advanced-stage Hodgkin lymphoma International Prognostication Index (A-HIPI). A-HIPI is a state-of-the-art clinical decision model to predict five-year progression-free and overall survival in adults with advanced-stage classic Hodgkin lymphoma using comprehensive individual patient data from international clinical trials and large prospective cancer registries. To enhance the use of A-HIPI, the team developed an online calculator to assist clinicians and patients in estimating individualized prognosis. This work was published in the Journal of Clinical Oncology (DOI: https://ascopubs.org/doi/full/10.1200/JCO.22.02473) simultaneously with an oral abstract presentation at the 2022 American Society of Hematology (ASH) Annual Meeting and Exposition.

    For the last 25 years, the International Prognostic Score (IPS) has been the most commonly used risk stratification tool for patients with advanced Hodgkin lymphoma, however, more modern tools to help inform individualized treatment and promote personalized cancer care are needed. Significant debate remains about the optimal treatment for Hodgkin lymphoma patients in the modern era, in part as its treatment comes at human cost, including an increased risk of treatment-related late effects like secondary malignant neoplasms and cardiovascular disease, compromised health-related quality of life, and the potential loss of young lives.

    A-HIPI is the inaugural work of the HoLISTIC project (Hodgkin Lymphoma International Study for Individual Care), building on detailed multi-source individual patient data from more than 15,000 Hodgkin lymphoma patients. A-HIPI development was performed on eight recent seminal phase 3 clinical trials conducted around the world. External validation was performed from contemporaneously treated patients in four “real-world” Hodgkin lymphoma registries across North America and Australia.

    HoLISTIC is spearheaded by Andrew M. Evens, DO, MBA, MSc, associate director for clinical services at Rutgers Cancer Institute and system director of medical oncology and oncology lead, RWJBarnabas Health and Susan K. Parsons, MD, MRP, medical director of the adolescent and young adult (AYA) program and research director of the Center for Health Solutions at Tufts Medical Center, who are co-principal investigators on the work.

    “Through continued collaboration with worldwide Hodgkin lymphoma clinical experts, decision scientists, statisticians, epidemiologists, and patient advocates, we’re one step closer to improving individualized prognostication and enhancing personalized medicine for Hodgkin lymphoma patients across all ages and disease stages,” notes Dr. Evens, who is also a professor of medicine at Rutgers Robert Wood Johnson Medical School, vice chancellor of clinical innovation and data analytics at Rutgers Biomedical and Health Sciences. “Through HoLISTIC, we will continue to develop innovative and evidence-based decision support models to guide Hodgkin lymphoma patients and their families and healthcare providers.” 

    “The A-HIPI model is an exciting first step for the HoLISTIC Consortium,” notes Dr. Parsons, who is also professor of medicine and pediatrics at Tufts University School of Medicine. “The next phase of the project will be significant, as we will extend the rigorous clinical modeling methodology to early-stage Hodgkin lymphoma and relapsed/refractory disease. We will also explore the impact of treatment selection and integrate PET imaging results and important biologic factors into the model.” The investigators plan to synthesize all of this information into a comprehensive and robust clinical decision model that estimates the likelihood of cure, life expectancy, post-acute and late effects, and quality-adjusted life expectancy for individual patients across varied treatment options.

    The dynamic and interactive decision support models generated by the HoLISTIC Consortium will guide individual patients and clinicians during initial diagnosis, relapse, and through survivorship in addition to serving as a strong basis for future health outcomes analyses, including patient preference and cost of care. The authors note limitations of the study include a lack of data in adults older than 65 who were treated in the clinical trials utilized for model development. Efforts are underway to identify other sources of information on older adults, as well as younger patients (adolescents and young adults), who are also often less represented in adult clinical trials.

    This work was presented as an oral presentation at the 2022 American Society of Hematology (ASH) Annual Meeting and Exposition and is supported in part by a National Cancer Institute Grant (R01CA262265). Author acknowledgements, disclosures and other information can be found here.  

    About Rutgers Cancer Institute of New Jersey  As New Jersey’s only National Cancer Institute-designated Comprehensive Cancer Center, Rutgers Cancer Institute, together with RWJBarnabas Health, offers the most advanced cancer treatment options including bone marrow transplantation, proton therapy, CAR T-cell therapy and complex surgical procedures. Along with clinical trials and novel therapeutics such as precision medicine and immunotherapy – many of which are not widely available – patients have access to these cutting-edge therapies at Rutgers Cancer Institute of New Jersey in New Brunswick, Rutgers Cancer Institute of New Jersey at University Hospital in Newark, as well as through RWJBarnabas Health facilities. To make a tax-deductible gift to support Rutgers Cancer Institute, call 848-932-8013 or visit www.cinj.org/giving. 

    About Tufts Medicine and Tufts Medical Center  Tufts Medicine is the parent organization of Tufts Medical Center, a world renowned 415-bed academic medical center in Boston that cares for the sickest patients in the region, includes a level one trauma center and one of the largest heart transplant centers in New England, and also serves as the principal teaching hospital for Tufts University School of Medicine. Tufts Medicine is also the parent organization of Lowell General Hospital, MelroseWakefield Healthcare, an expansive home care and hospice network, and a large clinically integrated physician network that cares for more than one million patients per year. The health system is dedicated to providing patients with the highest quality of care as close to home as possible.  

    ### 

    For patient appointments/inquiries – contact:  844-CANCERNJ (844-226-2376) 

     

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    Rutgers Cancer Institute of New Jersey

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  • Fred Hutch at ASH: Global insights on AML outcomes, COVID-19 and cancer, CD19 CAR T-cell therapy updates, latest on precision oncology — and more

    Fred Hutch at ASH: Global insights on AML outcomes, COVID-19 and cancer, CD19 CAR T-cell therapy updates, latest on precision oncology — and more

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    Newswise — SEATTLE — Dec. 1, 2022 — The 64th Annual Meeting and Exposition of the American Society of Hematology (ASH) will take place virtually and in person Dec. 10-13 in New Orleans, Louisiana.

    Below are highlights of Fred Hutchinson Cancer Center research to be presented, and you can follow Fred Hutch updates on Twitter #ASH22. You can also check out Fred Hutch’s booth 2622 in the exhibit hall.

    This year’s ASH press program highlights work below by Fred Hutch:

    Poster presentation: An analysis of the worldwide utilization of hematopoietic stem cell transplantation for acute myeloid leukemia Abstract: 3638 Presenter: Molly Tokaz Other Fred Hutch authors: Andrew Cowan and Mary-Beth Percival Sunday, Dec. 11, 6 p.m.

    A global study of use of transplantation for acute myeloid leukemia led by Fred Hutch fellow Dr. Molly Tokaz will be featured in a Dec. 7 virtual-only ASH briefing, “Building Solutions to Challenges in Health Equity.”

    Late-breaking session: Zanubrutinib demonstrates superior progression-free survival (PFS) compared with ibrutinib for treatment of relapsed/refractory chronic lymphocytic leukemia and small lymphocytic lymphoma (R/R CLL/SLL): Results from final analysis of ALPINE randomized phase 3 study Abstract: LBA-6 Senior author: Mazyar Shadman (On Twitter: @mshadman) Tuesday, Dec. 13, 8:30 a.m.

    A Dec. 12 media briefing on late-breaking abstracts will include an abstract co-authored by Fred Hutch’s Dr. Mazyar Shadman, a chronic lymphocytic leukemia and lymphoma physician-investigator. The abstract gives an update on a clinical trial assessing a next-generation Bruton tyrosine kinase inhibitor.

    Also on the press program, Dr. Stephanie Lee, former president of ASH, will moderate the Dec. 10 briefing “New Drugs, New Targets.” Dr. Lee is a transplant physician-scientist and expert in chronic graft-vs.-host-disease and holds the David and Patricia Giuliani/Oliver Press Endowed Chair in Cancer Research at Fred Hutch.

    Learn more in the ASH Annual Meeting press program.

    Poster presentation: Timing of PD-L1 Blockade with Durvalumab May Affect Outcomes of CD19 CAR-T Cell Therapy for Relapsed/Refractory Large B-Cell Lymphoma Abstract: 3316 Presenter: Alexandre Hirayama (On Twitter: @xanira) Sunday, Dec. 11, 6 p.m.

    Adding checkpoint blockades may make CAR T-cell therapy more effective against blood cancers, but combination trial results so far have been disappointing. This clinical trial evaluates the importance of timing of the therapies.

    Poster presentation: CAR T-cell therapy for relapsed or refractory large B-cell lymphoma using a fully human CD10-targeted single chain variable fragment: Results of a first-in-human phase I/II study Abstract: 4654 Presenter: Nicolas Gazeau (On Twitter: @NGazeau14) Monday, Dec. 12, 6 p.m.

    CAR T-cell therapies targeting the marker CD19 on cancer cells achieve high response rates in patients with relapsed or refractory large B-cell lymphoma, but durable responses are only achieved in 30-40% of patients. Based on clinical evidence showing lack of a durable response linked to a mouse-based component of the engineered cell, a phase I/II clinical trial is evaluating the effectiveness of the CAR T rebuilt with a human-based component instead. 

    Poster presentation: 3-Year follow-up analysis of ZUMA-5: a Phase 2 study of axicabtagene ciloleucel (Axi-Cel) in patients with relapsed/refractory (R/R) indolent non-hodgkin lymphoma (iNHL)

    Abstract: 4660 Co-author: David Maloney Monday Dec. 12, 6 p.m.

    This is a 3-year follow-up of the ZUMA-5 study, which shows that the CAR T-cell therapy called axi-cel demonstrated continued durable responses in patients with relapsed/refractory indolent non-hodgkin’s lymphoma (R/R iNHL) with improved survival observed in patients with marginal zone lymphoma. Late progression or death due to lymphoma or study treatment were uncommon and no new safety signals arose since the 2-year analysis. The research team also looked at biomarkers related to outcomes and found that preinfusion immunosuppressive Treg-related biomarkers were associated with relapse in patients with follicular lymphoma.

    Poster presentation: Circulating tumor DNA in untreated classical hodgkin lymphoma patients treated with pembrolizumab and chemotherapy: Dynamic response assessment and correlation with baseline metabolic tumor volume

    Abstract: 2913 Presenter: Ryan Lynch Sunday, Dec. 11, 6 p.m.

    This abstract presents updated results of a Fred Hutch single-center investigator-initiated clinical trial of the checkpoint inhibitor called pembrolizumab plus a chemotherapy for untreated classical Hodgkin lymphoma. The researchers continued to demonstrate a favorable safety profile with excellent efficacy (median follow up of 2.1 years, 2-year progression free survival of 97%). They also present new correlative data with circulating tumor DNA (ctDNA) for detection of minimal residual disease. It is possible that immunotherapy combinations may be associated with increased rates of uptake of residual F-fluorodeoxyglucose, which is a nonspecific imaging agent, and the team found that many of these patients have not had their cancer come back even several years later. In contrast, ctDNA was able to identify the lack of ctDNA clearance in the only patient who has relapsed today despite favorable initial PET scans. These findings indicate that ctDNA may represent a more sensitive and specific response assessment tool to be studied in larger datasets.

    Oral presentation: Self-reported experiences of adult hematopoietic cell transplantation survivors with COVID-19 vaccination and infection Abstract: 378 Presenter: Emily Liang (On Twitter: @emilyliangmd) Saturday, Dec. 10, 5:15 p.m.

    In a report of about 1700 stem cell transplant survivors, Fred Hutch clinicians found that vaccinated patients and their household contacts had a lower rate of COVID-19 infection compared with unvaccinated individuals (patients: 6% vs 68%, or 10-fold lower rate of infection; household contacts: 10% vs 46%, or 4-fold lower rate of infection) and were more likely to take additional safety precautions including masking and social distancing. The Fred Hutch team hopes the findings encourage others to receive the COVID-19 vaccination given the protective effect of vaccination and low rates of vaccine-related side effects.

    Poster presentation: A risk model for CML patients with COVID-19: Importance of molecular response in the context of age, comorbidities and country income Abstract: 4327 Presenter: Jerry Radich Monday, Dec. 12, 6 p.m.

    Researchers on the iCMLf CANDID study, a collaboration of 157 centers from 58 countries and with nearly 700 chronic myeloid leukemia patients participating, are looking for risk factors to predict which people with chronic myeloid leukemia are more likely to suffer worse outcomes from COVID-19. Dr. Jerry Radich, who holds the Kurt Enslein Endowed Chair at Fred Hutch, will report on the group’s findings, which show that age, molecular aspects of an individual’s CML, comorbidities and wealth of countries impact COVID-19 outcomes in CML patients.

    Oral presentation: Anti-leukemic activity of STRO-002 a novel folate receptor-α (FR-α)-targeting ADC in relapsed/refractory CBF2AT3-GLIS2 AML Abstract: 66 Presenter: Soheil Meshinchi Saturday, Dec. 10, 10:45 a..m.

    Acute myeloid leukemia remains one of the most difficult to treat pediatric cancers. Physician-scientist Dr. Soheil Meshinchi has led efforts to characterize the biology of this cancer in young patients and to identify targeted treatments that best suit their specific disease. At ASH, he will give an update on one such treatment, which was tested as part of Project Stella at Fred Hutch. His hope is that with detailed molecular testing of each patient followed by a targeted therapy, that children with the disease will go on to live long and healthy lives.

    Poster presentation: Umbrella trial in myeloid malignancies: The myeloMATCH national clinical trials network precision medicine initiative Abstract: 4080 Co-author: Jerry Radich Monday, Dec. 12, 6 p.m.

    Fred Hutch is part of an initiative led by the National Cancer Institute to help people newly diagnosed with acute myeloid leukemia and myelodysplastic syndromes to have a rapid (less than 3 days) testing of the clinical and molecular makeup of their disease and then be matched with treatment trials with promising therapeutic combinations. Fred Hutch, under the leadership of Dr. Jerry Radich, has been chosen to coordinate and perform the diagnostic and monitoring aspects of this nationwide initiative.

    Oral session: Allogeneic transplantation: Acute and chronic GVHD, immune reconstitution: Clinical studies exploring the immunobiology of HCT Abstract: 722 Moderator: Kate Markey (On Twitter: @katemarkey) Saturday, Dec. 10, 9:30 a.m.

    New insights – bolstered by emerging technological breakthroughs – on how the immune system recovers following transplantation are increasing our understanding of post-transplant complications like graft-versus-host disease. Fred Hutch’s Dr. Kate Markey, a physician-scientist and expert on how the microbiome affects recovery from transplantation, will moderate this session that includes clinical data from groups exploring T cell recovery after transplantation and clinical reports.

    Poster presentation: HSCs engraft in a stochastic pattern and form clonal pools following transplantation Abstract: 2527 Presenter: Stefan Radtke Sunday, Dec. 11, 6 p.m.

    Previous Fred Hutch studies discovered a subtype of hematopoietic stem cells that give rise to all other cells in the blood and immune systems, which could be a powerful therapeutic target. But because the cells are so rare, they’ve been difficult to study. Findings in this poster used a new type of bar coding to track individual cells and reveal some of the cellular dynamics that underlie their regenerative abilities.

    Poster presentation: Clinical and functional implications of MYC variants as a new class of pathogenic variants in AML Abstract: 1472 Presenter: Danielle Kirkey Saturday, Dec. 10, 5:30 p.m.

    Understanding the underlying genetics of pediatric acute myeloid leukemia can help determine how best to treat this difficult to treat disease. One of the genetic players is MYC, an oncogene involved in a majority of human cancers. In this work, Fred Hutch researchers defined the presence of different MYC variants and found that some occur in about 3.5% of pediatric patients with AML. The team did additional analyses to link MYC variants with other previously known high-risk features of AML and found those associations to be linked to clinical outcomes, which will allow for more nuanced stratification of a patient’s risk and will help determine optimal treatment regimens.

    Oral presentation: Treatment patterns and outcomes of patients with primary or secondary acute myeloid leukemia by type of site (academic or community government): A CONNECT® Myeloid Registry Study

    Abstract: 4023 Presenter: Bart Scott Monday, Dec 12, 6 p.m.

    This research was conducted to better understand management of secondary acute myeloid leukemias (SAML), which is a type of blood cancer that starts in white blood cells that grow in the bone marrow, often affecting people who have one of these blood cell diseases: myelodysplastic syndrome (MDS), myeloproliferative disorder (MPD) and aplastic anemia. The Fred Hutch team evaluated treatment patterns and outcomes in patients enrolled in the CONNECT® Myeloid Disease Registry. The findings indicate that outcomes for patients with AML in the registry are consistent with previously reported outcomes. This analysis suggests that contrary to commonly held perceptions, site of care does not affect overall patient outcomes. The clinically meaningful increase in overall survival in patients receiving an allogeneic hematopoietic stem cell transplant, regardless of primary or secondary AML further emphasizes the importance of providing patients with the opportunity for transplant.

    Poster presentation: Clinical outcome and treatment-related mortality in patients with acute myeloid leukemia treated at the Uganda Cancer Institute

    Abstract: 4031 Presenter: Clement Dove Okello Co-author: Soheil Meshinchi Monday, Dec 12, 6 p.m.

    A retrospective review of acute myeloid leukemia outcomes at the Uganda Cancer Institute examined factors associated with treatment-related mortality. Treatment of AML is similar across countries, but treatment-related mortality is significantly greater in low-income countries compared with high-income countries. This study by UCI and Fred Hutch researchers examined factors that could be contributing to greater mortality, in hopes of improving outcomes. Through the UCI-Fred Hutch Collaboration, Dr. Soheil Meshinchi, a Fred Hutch expert in AML, advised on the project.

    Poster presentation: Revised prognostic index for patients with acute myeloid leukemia and other high-grade myeloid neoplasms in first relapse

    Abstract: 1385 Presenter: Noam E. Kopmar Saturday, Dec 10, 5:30 p.m.

    Though many patients with acute myeloid leukemia will achieve a first complete remission, most patients will relapse. Fred Hutch researchers looked at predictors of relapse and examined methods to create an improved risk stratification model that will better predict likelihood of a second complete remission and overall survival after relapse. Through a better understanding of prognosis, providers may improve their ability to determine the optimal treatment approach and also better inform the counseling provided to patients regarding prognosis.

    Poster presentation: Prognostic significance of chromosomal genomic array testing in adults with newly diagnosed acute lymphoblastic leukemia

    Abstract: 4145 Presenter: Noam E. Kopmar Saturday, Dec 12, 6 p.m.

    This project led by members of the acute leukemia and myeloid malignancies research group at Fred Hutch is aimed at improving prognostic capabilities at the time of either a new diagnosis or at the time of first relapse, correlating chromosomal genomic array testing results with key demographic and outcomes data. Having a better understanding of prognosis may improve the ability of providers to determine the optimal treatment approach and also better inform the counseling that is provided to patients regarding prognosis.

    The disease-killing T cells of the immune system develop their capabilities in a small, butterfly-shaped gland in the chest called the thymus. The thymus can regenerate to keep its immune function strong, but it wears out from stress, infection and aging. At ASH, Fred Hutch researchers will report their latest findings on how to repair the thymus:

    Oral presentation: Interleukin-18 suppresses regeneration of the thymus

    Abstract: 483 Presenter: David Granadier Co-author Jarrod Dudakov (On Twitter: @Dudakov_Lab) Monday, Dec 12, 4:30 p.m.

    Research by graduate student David Granadier in Dr. Jarrod Dudakov’s lab implicates the cytokine IL-18 in regulating the ability of the thymus to repair itself. This presentation will these latest insights. More on the signaling pathways involved in thymic regeneration and their implications for therapeutics in a Fred Hutch news story.

    Poster presentation: The zinc-sensing receptor GPR39 is a master regulator of immune reconstitution after bone marrow transplant in the thymus and in the bone marrow

    Abstract: 4581 Presenter: Lorenzo Iovino Co-author Jarrod Dudakov (On Twitter: @Dudakov_Lab) Monday, Dec 12, 6 p.m.

    Zinc is well-known for its immune-boosting properties, and recently Dr. Lorenzo Iovino in Dudakov’s lab at Fred Hutch revealed how zinc supports immune function through the thymus. Iovino will give an update on the work and how it could be used to improve treatments for cancer patients.

    Note: Fred Hutch and the scientists who contributed to these discoveries may stand to benefit from their future commercialization.

    The clinical trials referenced above involve investigational products and/or therapies that have not been approved for commercial marketing by the U.S. Food and Drug Administration or any other regulatory authority. Results may vary and encouraging results from early stage clinical trials may not be supported in later stage clinical trials.  No conclusions should be drawn from the information in this report about the safety, efficacy, or likelihood of regulatory approval of these investigational products and/or therapies.

    # # #

    Fred Hutchinson Cancer Center unites comprehensive care and advanced research to provide the latest cancer treatment options and accelerate discoveries that prevent, treat and defeat cancer and infectious diseases worldwide.

    Based in Seattle, Fred Hutch is an independent, nonprofit organization and the only National Cancer Institute-designated cancer center in Washington. We have earned a global reputation for our track record of discoveries in cancer, infectious disease and basic research, including important advances in bone marrow transplantation, HIV/AIDS prevention, immunotherapy and COVID-19 vaccines. Fred Hutch operates eight clinical care sites that provide medical oncology, infusion, radiation, proton therapy and related services and has network affiliations with hospitals in four states. Fred Hutch also serves as UW Medicine’s cancer program.

    Please note that our organization was renamed Fred Hutchinson Cancer Center in April 2022, following the merger of long-time partners, Fred Hutchinson Cancer Research Center and Seattle Cancer Care Alliance. 

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    Fred Hutchinson Cancer Center

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  • Shorter Course of Radiation Therapy Yields Comparable Results for Patients with Non-Metastatic Soft Tissue Sarcoma

    Shorter Course of Radiation Therapy Yields Comparable Results for Patients with Non-Metastatic Soft Tissue Sarcoma

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    Newswise — HOUSTON – Patients with non-metastatic soft tissue sarcoma (STS) who need pre-operative radiation therapy can safely receive hypofractionated treatment over three weeks instead of five, with comparable tumor control and no increased risk of major complications in wound healing, according to researchers at The University of Texas MD Anderson Cancer Center.

    Results from the study, led by Ashleigh Guadagnolo, M.D., professor of Radiation Oncology, were published today in The Lancet Oncology. Guadagnolo also presented results at the 2022 American Society for Radiation Oncology (ASTRO) Annual Meeting. 

    On the single-arm, non-randomized trial, patients received hypofractionated radiation therapy, consisting of higher daily radiation therapy doses per treatment over fewer days relative to conventional therapy. Thirty-one percent of patients developed major wound complications within 120 days of surgery, while local tumor control was 93% at two-year follow-up — both comparable to historically reported rates with the longer treatment course.

    “Our data indicate the three-week regimen offers patients a likely safe and effective alternative to the current standard of care with comparable outcomes in disease control and no increased risks of major wound complications,” Guadagnolo said. “We are excited by the current results of this study, which demonstrate the value of a hypofractionated approach to radiation therapy, which is more convenient for patients.”

    A major side effect of pre-operative radiation therapy in patients with non-metastatic STS is an increased risk of wound-healing complications after surgery. Patients have a heightened risk of needing a second operation for wound repair, extensive wound management and readmission to the hospital.  

    On the current study, no patients experienced a serious adverse event or a grade 3 acute skin toxicity while on the study. The 31% rate of major wound complications is comparable to the historically observed 35% rate in patients treated with the standard five-week regimen.

    “Research shows that patients receiving their treatment at cancer centers with sarcoma specialists have better survival and functional outcomes. Being able to shorten our patients’ treatment time from five to three weeks may improve care accessibility because patients would be able to reduce their time away from home if they do not live near a sarcoma specialty center,” Guadagnolo said.

    The trial enrolled a total of 120 patients over the age of 18 with non-metastatic STS who had not previously undergone radiation therapy. All patients had STS in the extremity or superficial trunk; 65% of participants had lower extremity tumors; 17% had upper extremity tumors and 18% had tumors in the trunk.

    All patients were treated with a three-week course of radiation consisting of 15 daily fractions of 2.85 Gray (Gy), totaling 42.75 Gy. The current standard dose is 50 Gy in 25 daily fractions, or a five-week course. Radiation therapy was followed by surgery four to eight weeks later. Researchers assessed major wound complications within 120 days of surgery among patients treated on the trial.

    Long-term side effects, oncologic and functional outcomes using the hypofractionated regimen still are being assessed.

    The research was supported by the National Cancer Institute (P30 CA016672). A full list of collaborating authors and their disclosures can be found with the full paper here.

    – 30 –

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    University of Texas M. D. Anderson Cancer Center

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  • NCCN Working with Medlive to Advance High-Quality Cancer Care in China and Worldwide

    NCCN Working with Medlive to Advance High-Quality Cancer Care in China and Worldwide

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    Newswise — PLYMOUTH MEETING, PA, UNITED STATES [November 2, 2022] — The National Comprehensive Cancer Network® (NCCN®)—an alliance of leading cancer centers in the United States—is announcing a new collaboration with Medlive to share NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) in China at nccnchina.org.cn. NCCN Guidelines® are the recognized standard for clinical direction and policy in cancer management and the most thorough and frequently-updated clinical practice guidelines available in any area of medicine.

    The current library of 84 evidence-based, expert consensus practice guidelines cover 97% of cancer cases affecting patients—with specific treatment recommendations for nearly every type of cancer, plus supportive care and prevention—and are updated at least once-a-year. There are also 65 patient-focused versions of the guidelines for patients and caregivers. All are now available at quicker in-country download speeds with a one-step registration process, also via guide.medlive.cn/NCCN on computer or the Medlive APP on smartphone. These resources will also be translated into Chinese in the future.

    “We are committed to making sure providers and patients have access to the most up-to-date standards in cancer care around the world,” said Robert W. Carlson, MD, Chief Executive Officer, NCCN. “At NCCN, we believe that everyone worldwide should benefit from the rapidly expanding knowledge on how to treat cancer most effectively; and we work tirelessly to make that happen. We are proud to collaborate with Medlive on this important project.”

    Although NCCN is a U.S.-based organization, NCCN resources are accessed and utilized throughout the world. Nearly half of the 1.5 million registered users viewing NCCN Guidelines at NCCN.org or via the Virtual Library of NCCN Guidelines® app are located outside of the U.S. China is currently the third-highest country for clinical practice guideline downloads, with more than 400,000 per year. This new in-country platform for guidelines is expected to increase that number significantly.

    “We are happy to introduce a new home for NCCN resources in China here on our Medlive platform, providing doctors with faster access to NCCN Guidelines,” said Tian Lixin, President, Medlive. “This collaboration will help oncologists in China to reference the widely-recognized NCCN Guidelines, so all patients can receive high-quality, effective, and efficient treatment according to the latest evidence-based expert consensus standards.”

    “Both NCCN and Medlive recognize the importance of collaboration and mutual learning,” said Xin Jiangtao, Vice President, Medlive. “We are pleased to use this platform for knowledge sharing between oncology circles in Asia and the United States, ultimately improving care for patients everywhere.”

    The collaboration will focus on providing the full English-language library of NCCN Guidelines on Medlive’s platform (in addition to their longtime home at NCCN.org), with Chinese translations to follow in the near future. The new website specifically for NCCN on Medlive was first announced on June 15, 2022 with a live conference hosted by Medlive. The full broadcast is available on-demand at class.medlive.cn/class/live/close/68550.

    Visit NCCN.org/global to learn more about NCCN’s work to improve cancer outcomes around the world. Join the conversation online with the hashtag #NCCNGlobal.

    # # #

    About the National Comprehensive Cancer Network

    The National Comprehensive Cancer Network® (NCCN®) is a not-for-profit alliance of leading cancer centers devoted to patient care, research, and education. NCCN is dedicated to improving and facilitating quality, effective, equitable, and accessible cancer care so all patients can live better lives. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) provide transparent, evidence-based, expert consensus recommendations for cancer treatment, prevention, and supportive services; they are the recognized standard for clinical direction and policy in cancer management and the most thorough and frequently-updated clinical practice guidelines available in any area of medicine. The NCCN Guidelines for Patients® provide expert cancer treatment information to inform and empower patients and caregivers, through support from the NCCN Foundation®. NCCN also advances continuing education, global initiatives, policy, and research collaboration and publication in oncology. Visit NCCN.org for more information and follow NCCN on Facebook @NCCNorg, Instagram @NCCNorg, and Twitter @NCCN.

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    National Comprehensive Cancer Network(r) (NCCN(r))

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  • FDA Approves Oral MEK Inhibitor Cobimetinib for Histiocytic Neoplasms, Research Led by Memorial Sloan Kettering Cancer Center

    FDA Approves Oral MEK Inhibitor Cobimetinib for Histiocytic Neoplasms, Research Led by Memorial Sloan Kettering Cancer Center

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    Newswise — Memorial Sloan Kettering Cancer Center (MSK) announced today that the U.S. Food and Drug Administration (FDA) has approved the oral MEK inhibitor drug cobimetinib (Cotellic®) for the treatment of adult patients with the family of blood diseases known as histiocytic neoplasms (HN). These diseases include Erdheim-Chester disease, Rosai-Dorfman disease, and Langerhans cell histiocytosis. Cobimetinib is an oral inhibitor of MEK1 and MEK2, currently approved to treat melanoma.

    The approval was granted based on data collected by MSK in collaboration with Genentech, a member of the Roche Group, from a single-institution phase 2 trial of single-agent cobimetinib for adults with histiocytic disorders. A rarity in the world of cancer research, the clinical trial that led to the approval was conducted solely at MSK.

    This work builds upon the approval of vemurafenib (Zelboraf®) in 2017 for the treatment of Erdheim-Chester disease, a type of histiocytosis. Vemurafenib targets the BRAF V600E mutation found in more than half of histiocytosis cases and was the first targeted therapy to be approved based on a basket trial, a novel tumor-agnostic clinical trial design pioneered at MSK.

    “The approval of cobimetinib represents the collective hard work of several years of investigation by many MSK researchers. There have been tremendous advances in the field of rare cancers as a result of research and trials conducted at MSK, and this approval is an excellent example of a practice-changing outcome,” said Eli L. Diamond, MD, neuro-oncologist and neurologist at MSK and principal investigator of the trial. “There has always been an unmet need for patients with histiocytosis, and we are thrilled that with this approval, these patients will now have access to a viable treatment option.”

    Histiocytosis is a family of blood diseases that affect both children and adults. These rare diseases are estimated to affect approximately 1 to 2 out of 200,000 people each year. The disease can infiltrate any part of the body, but most often presents in the brain. Before now, available treatment options for most adults with HN were limited and associated with poor long-term tolerance. Doctors at MSK care for more adults with histiocytosis than any other hospital in the United States.

    In October 2019, the FDA announced Breakthrough Therapy Designation to cobimetinib for MEK inhibition in HN, based on a trial published in Nature in March 2019 by a team of MSK researchers led by Dr. Diamond; Omar Abdel-Wahab, MD, hematologic oncologist and Director of the Center for Hematologic Malignancies at MSK; and David Hyman, MD, former Chief of the Early Drug Development Service at MSK. The team used genetic sequencing test MSK-IMPACT®, created by the Department of Pathology at MSK, to determine patients’ mutations.

    “Until now, no standard therapy has existed for the 50% of histiocytosis patients without the BRAF V600E mutation,” said Dr. Abdel-Wahab. “The research pioneered at MSK has led to a viable treatment option for adult patients who harbor this mutation. Looking ahead, we are working on advancing treatment options for pediatric patients with histiocytosis as we have done in adults.”

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    Memorial Sloan Kettering Cancer Center

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  • Do Pancreatic Cysts Become Cancerous?

    Do Pancreatic Cysts Become Cancerous?

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    Newswise — New Brunswick, N.J., November 1, 2022 – It’s not unusual for cysts to form in the pancreas,  an important organ that produces enzymes that help digest food, and it secretes hormones—such as insulin—that help regulate metabolism. Although some pancreas cysts are benign, the majority are pre-cancerous and are the most common identifiable precursor to pancreatic cancer. Russell Langan, MD, FACS, FSSO, surgical oncologist at Rutgers Cancer Institute of New Jersey,  the state’s leading cancer center and only NCI-designated Comprehensive Cancer Center, chief of Surgical Oncology and Hepatopancreatobiliary Surgery at Cooperman Barnabas Medical Center, an RWJBarnabas Health facility, and assistant professor of surgery at Rutgers Robert Wood Johnson Medical School, shares more information on monitoring pancreatic cysts and pancreatic cancer.

    The Difference between Pancreatic Cancer and Cysts

    According to the National Cancer Institute, pancreatic cancer is the fourth leading cause of cancer death in the United States. A history of smoking, diabetes and chronic pancreatitis and obesity are risk factors for developing the disease. Further, the risk of pancreatic cancer is higher if there is either a family history of pancreatic cancer or a history of certain genetic syndromes. Pancreatic cysts are fluid-filled growths that develop in the pancreas. Most develop for no apparent reason are incidentally identified but do require surveillance.

    Their Link to Pancreatic Cancer

    Unlike other cysts such as those on the ovaries, liver or kidneys, pancreatic cysts do have the potential to progress to pancreatic cancer over time. It is widely believed that certain pancreatic cysts represent a field defect of the pancreas and that the risk of developing a pancreas cancer is not only within the cyst but rather the entire gland itself. 

    Finding Pancreatic Cysts

    Pancreatic cysts often don’t cause symptoms, so they’re frequently found during an imaging scan for something else. Once identified, patients and doctors are encouraged to refer to pancreatic care teams where the characteristics of the cyst, pancreas, family history and other risk factors can all be assessed by a pancreas multidisciplinary team.

    Preventative Medicine at its Best

    When pancreatic cysts are followed and surveyed appropriately, intervening at appropriate times can reduce the risk of developing pancreas cancer. Cooperman Barnabas Medical Center has pioneered one of the first cloud-based data management platforms in the nation to identify, track and monitor patients with pancreatic cysts. Through the program, patients are identified and offered consultation with our pancreas care team.  In doing this, the appropriate evidence based follow-up imaging or endoscopy is performed regularly to monitor the cysts and the surrounding pancreas.

    To learn more visit rwjbh.org/beatcancer or call 844-CANCERNJ (844-226-2376).

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    Rutgers Cancer Institute of New Jersey

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  • MD Anderson’s Guillermina Lozano Receives AAMC Award for Distinguished Research in the Biomedical Sciences

    MD Anderson’s Guillermina Lozano Receives AAMC Award for Distinguished Research in the Biomedical Sciences

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    Newswise — HOUSTON ― In recognition of her trailblazing work uncovering the mechanisms of the p53 tumor suppressor, Guillermina “Gigi” Lozano, Ph.D., chair of Genetics at The University of Texas MD Anderson Cancer Center, has received the 2022 Award for Distinguished Research in the Biomedical Sciences by the Association of American Medical Colleges (AAMC).

    Since its inception in 1947, the AAMC Award for Distinguished Research in the Biomedical Sciences has annually honored an individual or team of two individuals whose research has contributed to significant scientific discoveries benefitting human health and well-being, who participate in research beyond their own work through mentorship or review panels, and whose standards of professional ethics and scientific integrity are of the highest caliber. Lozano is the second MD Anderson researcher to be selected for this award, with James Allison, Ph.D., honored in 2014.

    “Gigi’s key discoveries in the field of cancer biology are of tremendous importance, enabling a deeper understanding of the mechanisms that drive tumor development and treatment response. These breakthroughs are necessary for advancing the field and improving the care we bring to our patients,” said Giulio Draetta, M.D., Ph.D., chief scientific officer. “Her commitment to research excellence strengthens our entire MD Anderson community, and we applaud her for this well-deserved recognition.”

    Lozano is internationally recognized as one of the world’s foremost cancer researchers. She was the first to establish p53 as a transcriptional activator of other genes and highlighted its mutation or deletion as a hallmark of more than 90% of cancers. She also identified the physiological roles of the Mdm2 and Mdm4 proteins as gatekeepers in cancer development and in regulating p53, providing the backbone for potentially using Mdm2/4 inhibitors as a novel targeted therapy approach .

    “I am flattered to be recognized for our work on the p53 tumor suppressor pathway and want to thank members of my laboratory for all of their contributions,” Lozano said. “I look forward to continuing our exciting research and advancing new discoveries that will bring us closer to our mission to end cancer.”

    Lozano also discovered the key mechanism through which breast cancers with mutant p53 respond better to chemotherapy than those with wild-type p53, and she led the development of laboratory models of mutant p53 that more accurately represent breast and pancreatic cancers. The Lozano laboratory at MD Anderson remains focused on understanding the effects of wild-type or mutant p53 on the tumor microenvironment and on genomic stability in cancer development and progression.

    Lozano graduated magna cum laude with degrees in biology and mathematics from The University of Texas Rio Grande Valley. She received her Ph.D. in biochemistry from Rutgers University and the University of Medicine and Dentistry of New Jersey, continuing to Princeton University for a postdoctoral fellowship. She joined MD Anderson in 1987 and has published 261 articles in peer-reviewed journals, reviews and book chapters over the course of her 35 years at the institution, rising to her current position as chair of the department of Genetics. She has also mentored many young scientists, with 33 graduate students receiving their M.S. and Ph.D. degrees under her direction and 29 postdoctoral fellows having trained in her lab.

    Lozano is an elected fellow of the American Association for the Advancement of Science (AAAS) and the American Association for Cancer Research (AACR) Academy. She has been elected to the National Academy of Medicine, the National Academy of Sciences, and the American Academy of Arts and Sciences. Among her many honors, she has received the Hubert L. Olive Stringer Distinguished Chair in Oncology in Honor of Sue Gribble Stringer in 2018, the AACR-Minorities in Cancer Research Jane Cooke Wright Lectureship and AACR-Women in Cancer Research Charlotte Friend Lectureship awards, and the 2018 MD Anderson President’s Leadership Award for Advancing Women and Minority Faculty.

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    University of Texas M. D. Anderson Cancer Center

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  • MD Anderson hosts Leading Edge of Cancer Research Symposium

    MD Anderson hosts Leading Edge of Cancer Research Symposium

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    Newswise — HOUSTON ― The University of Texas MD Anderson Cancer Center will host its virtual Leading Edge of Cancer Research Symposium from November 17-18, 2022, featuring presentations and discussions on important topics in discovery and translational research that will drive the next wave of cancer breakthroughs. The event also includes a virtual poster session; interested researchers are encouraged to submit abstracts by October 24, 2022.

    The Leading Edge of Cancer Research Symposium will include keynote presentations from Tyler Jacks, Ph.D., president of Break Through Cancer and the David H. Koch Professor of Biology at the Massachusetts Institute of Technology; Alan Ashworth, Ph.D., the E. Dixon Heise Distinguished Professor in Oncology at the University of California San Francisco; and Simona Colla, Ph.D., associate professor of Leukemia at MD Anderson.

    The event also will feature a panel discussion, “The Patient Is the Focus: Breakthroughs from Bench to Bedside, Clinical and Multiomics Integration and High Value Cancer Care.” Additional sessions will focus on the following topics:

    • Clonal Expansion in Normal and Pathological Tissues: It’s All a Matter of Fitness
    • Unleashing the Immune System to Develop Therapeutic Strategies
    • Integrated Immune-Microbiome Biomarker Discovery
    • Clinical Data Science

    “In the spirit of cooperation, MD Anderson is excited to host the Leading Edge of Cancer Research Symposium, and we welcome cancer researchers to participate in sharing cutting-edge discoveries that enable fruitful scientific discussions and innovations in the field,” said Giulio Draetta, M.D., Ph.D., chief scientific officer. “This collaborative environment is accessible to everyone, and we encourage our peers to join our collective mission to end cancer as we strive to bring the best science to our patients.”

    For more than 80 years, MD Anderson has advanced impactful research across the spectrum of cancer science. The institution has cultivated a unique environment that allows discoveries to be translated directly to the clinic and, simultaneously, insights from the clinic to inform studies in the lab. This seamless collaborative cycle enables significant breakthroughs at an unmatched pace.

    The Leading Edge of Cancer Research Symposium brings together the global research community to engage in beneficial discussions and to stimulate innovative research that will improve patients’ lives. More information on the symposium, including a full agenda and links to register or submit posters, can be found at MDAnderson.org/ResearchSymposium.

     

     

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    University of Texas M. D. Anderson Cancer Center

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  • Cancer Research Institute to Honor Scientists for Groundbreaking Discoveries Leading to New Immune-Based Strategies That Target Gasdermins in Cancer Treatment

    Cancer Research Institute to Honor Scientists for Groundbreaking Discoveries Leading to New Immune-Based Strategies That Target Gasdermins in Cancer Treatment

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    Newswise — NEW YORK, September 27, 2022 – The Cancer Research Institute (CRI), a nonprofit organization dedicated to harnessing the immune system’s power to control and potentially cure all types of cancer, will confer its prestigious 2022 William B. Coley Award for Distinguished Research in Basic and Tumor Immunology on four scientists for their collective work that revealed the role of the pore-forming gasdermins in pyroptosis and promotion of anti-tumor immunity, setting the stage for targeting gasdermins in cancer therapeutics. 

    Judy Lieberman, M.D., Ph.D., and Hao Wu, Ph.D., of Boston Children’s Hospital and Harvard Medical School, Feng Shao, Ph.D., of the National Institute of Biological Sciences, Beijing, and Vishva Dixit, M.D., of Genentech will receive their Coley Awards during an evening ceremony taking place Tuesday, September 27, at The New York Hilton Midtown, where CRI with its partners the European Network for Cancer Immunotherapy (ENCI) and the American Association for Cancer Research (AACR) will host their four-day International Cancer Immunotherapy Conference. 

    Gasdermins (GSDMs) are a family of proteins originally identified and named from their expression in the gastrointestinal tract and the skin. In 2015, Dixit and Shao’s groups discovered that gasdermin D (GSDMD) is a substrate of inflammatory caspases, which are activated downstream of the immune system’s inflammasomes when they sense pathogen- or damage-associated molecules. GSDMD is the key executioner of inflammasome-induced inflammatory cell death called pyroptosis in immune sentinel cells and is responsible for the secretion of IL-1 family cytokines. Pyroptosis is a highly immunogenic form of cell death, and pyroptosis in cancer in theory could result in the release of danger-associated molecules and neoantigens to alert the immune system and promote antitumor immunity.

    In 2016, Lieberman and Wu, and Shao, went on to demonstrate the mechanisms by which gasdermins effect cell death. Specifically, they discovered that upon processing by inflammatory caspases, the GSDMD N-terminal domain (GSDMD-NT) binds acidic lipids and forms cell membrane pores that are responsible for cell death. These pores also release mature IL-1 family cytokines and other danger signals, including chemokines, which recruit and activate immune cells to the site of danger. The requirement for binding to acidic lipids for GSDMD pore formation and the enrichment of these lipids in the inner leaflet of the cytoplasmic membrane suggested that GSDMD kills from within the cell but does not harm bystander mammalian cells. Lieberman and Wu further showed that GSDMD kills bacteria upon activation by binding to an acidic lipid called cardiolipin on bacterial membranes. Shao developed a crystal structure of a GSDM family member, mouse GSDMA3, showing that GSDMD-NT is autoinhibited by the GSDMD C-terminal region in full-length GSDMD. Dixit and other groups subsequently published their identification of the pore-forming activity of GSDMD.

    “Discovery of the pore-forming activity of GSDM proteins changed the definition of pyroptosis from a ‘fiery death’ induced by inflammasome activation to GSDM-mediated lytic cell death, opening the search for other proteolytic pathways for activating GSDMD and other GSDMs,” said Frederick W. Alt, Ph.D., a Howard Hughes Medical Institute Investigator and director of the Program in Cellular and Molecular Medicine at Boston Children’s Hospital and a member of the CRI Scientific Advisory Council.

    The direct relationship to cancer of another gasdermin, GSDME, became clear in a series of papers authored by Lieberman and Wu, and Shao. They showed that the expression of GSDME is often repressed or mutated to lose its function in cancers while expression of GSDME converts noninflammatory apoptosis to inflammatory pyroptosis, effectively altering immunogenically “cold” tumors that do not ignite an anticancer immune response into “hot” tumors that attract killer cytotoxic T lymphocytes and natural killer cells. Shao showed that delivery of gasdermins via cancer-targeting nanoparticles can result in cancer cell pyroptosis in mice, resulting in the suppression of entire tumor grafts, not only the targeted tumor tissue because the treatment activated an effective adaptive immune response to the tumor. 

    “The groundbreaking molecular and mechanistic studies carried out by Lieberman and Wu, Shao, and Dixit along with the preclinical development of effective therapeutics that can convert immunologically cold tumors to hot have made possible therapeutic interventions that specifically activate GSDMs in cancer cells to promote antitumor immunity and responsiveness to checkpoint blockade immunotherapy,” said Jill O’Donnell-Tormey, Ph.D., CEO and director of scientific affairs at the Cancer Research Institute.

    In addition to presenting the 2022 William B. Coley Award, the ceremony will also feature the presentation of the 2022 Frederick W. Alt Award for New Discoveries in Immunology to David Masopust, Ph.D., the McKnight University Professor and a Howard Hughes Medical Institute Faculty Scholar in the Department of Microbiology and Immunology at the University of Minnesota, for his body of research focused on T cell development and biology, primarily memory T cell development and behavior. The Alt Award is given to a former CRI postdoctoral fellow whose work has made a significant impact on the fields of immunology or tumor immunology. Masopust received CRI funding while carrying out postdoctoral research in the laboratory of renowned immunologist and virologist Rafi Ahmed, Ph.D., at Emory University, from 2002-2005.

     

    About the William B. Coley Award for Distinguished Research in Basic and Tumor Immunology
    The Cancer Research Institute established this award in 1975 in honor of Dr. William B. Coley, now regarded as the Father of Cancer Immunotherapy, whose daughter Helen Coley Nauts (1907-2001) founded the Cancer Research Institute. Considered CRI’s highest scientific accolade as well as a predictor of more widely recognized scientific honors including the Lasker Award and Nobel Prize, the Coley Award has been given to 119 immunologists and tumor immunologists including the 2022 recipients. See past Coley Award winners here.

    About Cancer Research Institute
    The Cancer Research Institute (CRI), founded in 1953, is a highly rated U.S. nonprofit organization dedicated exclusively to saving more lives by fueling the discovery and development of powerful immunotherapies for all cancers. Guided by a world-renowned Scientific Advisory Council that includes four Nobel laureates and 27 members of the National Academy of Sciences, CRI has invested $500 million in support of research conducted by immunologists and tumor immunologists at the world’s leading medical centers and universities and has contributed to many of the key scientific advances that demonstrate the potential for immunotherapy to change the face of cancer treatment. To learn more, go to cancerresearch.org.

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    Cancer Research Institute

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