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Tag: National Cancer Institute (NCI)

  • Study could help explain why certain brain tumors don’t respond well to immunotherapy

    Study could help explain why certain brain tumors don’t respond well to immunotherapy

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    BYLINE: Denise Heady

    Newswise — A study led by researchers at the UCLA Jonsson Comprehensive Cancer Center sheds new light on why tumors that have spread to the brain from other parts of the body respond to immunotherapy while glioblastoma, an aggressive cancer that originates in the brain, does not.

    In people with tumors that originated in other parts of the body but spread to the brain, treatment with a type of immunotherapy called immune checkpoint blockade appears to elicit a significant increase in both active and exhausted T cells — signs that the T cells have been triggered to fight the cancer. The reason the same thing doesn’t occur in people with glioblastoma is that anti-tumor immune responses are best initiated in draining lymph nodes outside of the brain, and that process does not occur very effectively in glioblastoma cases.

    To date, immunotherapy has not been effective in treating glioblastoma, but it has been shown to slow or even eradicate other types of cancer, such as melanoma, which frequently metastasizes to the brain.

    The new research, published in the Journal of Clinical Investigation, could help improve the effectiveness of immunotherapy for people with brain tumors and it could suggest new paths in the effort to help develop more effective therapies.

    “If we’re going to try to develop new therapies for solid tumors, like glioblastoma, which are not typically responsive, we need to understand the tumor types that are responsive, and learn the mechanisms by which that happens,” said the study’s senior author, Robert Prins, a professor of molecular and medical pharmacology and of neurosurgery at the David Geffen School of Medicine at UCLA.

    The researchers studied the immune cells obtained from nine people with metastatic brain tumors who had been treated with immune checkpoint blockade — which works by harnessing the body’s immune system to destroy cancer cells — and compared their observations with immune cells taken from 19 patients with brain metastases that not been treated with immunotherapy.

    They used a technique called single-cell RNA sequencing to examine the genetic material in both sets of samples, and then compared the data to previously published analyses of 25 recurrent glioblastoma tumors to better understand the effect the immunotherapy had on T cells.

    “We really were trying to figure out which immune cells are changing in the more responsive tumors in order to better explain the higher response rate to the treatment,” said the study’s co-first author, Lu Sun, a project scientist in the Geffen School of Medicine’s neurosurgery department. “No study has comprehensively examined the differential effect of immune checkpoint blockade treatment on these two types of brain tumors before.”

    In the tumors that had spread to the brain, the researchers saw that the T cells had specific characteristics associated with fighting tumors entering the brain, most likely due to a more effective priming step that occurs outside of the brain.

    Before traveling to the brain, T cells are first activated in the lymph nodes. During this process, a type of immune cells called dendritic cells share information about the tumor to T cells so they can better attack the tumor. This priming process, however, doesn’t work very effectively when doctors attempt to use immune checkpoint blockade for treating glioblastoma.

    The researchers also found that a specific subgroup of those exhausted T cells was associated with longer overall survival in people whose cancer had metastasized to the brain.

    “We found quite a significant difference between the two types of brain tumors and how they respond to immunotherapies,” said study author Dr. Won Kim, surgical director of UCLA Health’s brain metastasis program and a member of the Jonsson Cancer Center. “There was a tremendous number of T cell lymphocytes that were found within brain metastases following immunotherapy, and while the number of T cell lymphocytes also increased in glioblastoma patients, it wasn’t anywhere near the same extent.”

    Prins, who is also a researcher at the Jonsson Cancer Center, said that finding “suggests that enhancing the activation and presentation of T cells by dendritic cells could be a potential treatment strategy.”

    In future studies, the researchers plan to analyze data from a larger, more uniform group of people who were diagnosed with melanoma that had spread to the brain.

    The study’s other co-first author is Jenny Kienzler, who was a UCLA fellow in neurosurgery when the research was conducted. Other UCLA authors are Jeremy Reynoso, Alexander Lee, Eileen Shiuan, Shanpeng Li, Jiyoon Kim, Lizhong Ding, Amber Monteleone, Geoffrey Owens, Dr. Richard Everson, David Nathanson, Dr. Timothy Cloughesy, Gang Li, Dr. Linda Liau and Willy Hugo.

    The research was supported by grants from the National Institutes of Health Specialized Programs of Research Excellence in Brain Cancer, National Cancer Institute, National Institutes of Health National Center for Advancing Translational Science, Parker Institute for Cancer Immunotherapy, Brain Tumor Funder’s Collaborative and Cancer Research Institute.

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    University of California, Los Angeles (UCLA), Health Sciences

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  • Transcription Factors Contribute to Subtypes of Colorectal Cancers

    Transcription Factors Contribute to Subtypes of Colorectal Cancers

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    Newswise — New research in colorectal cancers directed by investigators at the Johns Hopkins Kimmel Cancer Center suggests that expression of transcription factors — proteins that help turn specific genes on or off by binding to nearby DNA — may play a central role in the degree of DNA methylation across the genome, contributing to the development of different subtypes of these cancers. Methylation is a process in which certain chemical groups attach to areas of DNA that guide genes’ on/off switches. Studying the expression of these transcription factors in patients with colorectal cancers could reveal biomarkers to help determine overall survival in people with a subgroup of colorectal cancers who generally have better survival rates and, importantly, respond better to immune checkpoint therapy — a type of immunotherapy that releases restraints that cancer cells place on the immune response — and other treatments. Similar patterns of transcription factor expression could be seen by the researchers even in precancerous polyps, and could potentially be used by physicians to determine which patients need closer follow-up to prevent cancer development.

    A description of the work was published online July 24 in the journal Proceedings of the National Academy of Sciences.

    Aberrant DNA methylation is a well-known phenomenon occurring in cancers, explains senior study author Hariharan Easwaran, Ph.D., M.Sc., an associate professor of oncology at the Johns Hopkins Kimmel Cancer Center, but the degree of DNA methylation varies in cancers of the same tissue type. Some colon and other cancers have a very high degree of DNA methylation gains while others have much lower frequency of DNA methylation gains, he says. Traditionally, these have been described in an area of the genome known as a promoter region, which helps launch the transcription process. The exact mechanisms underlying these changes have not been clear.

    In a series of laboratory studies of genetic material taken from tubular adenomas (precancerous polyps in the colon) and colon tumors, the researchers linked cancer-specific transcription factor expression alterations to methylation alterations in colorectal cancers and their premalignant precursor lesions, which provided insights into the origins and evolution of different molecular subtypes of colorectal cancers.

    Specifically, researchers observed that some regions of the genome undergoing increased methylation tend to have binding sites for transcription factors that are downregulated, or have low expression. In some types of colon cancer, based on the types of genetic alterations associated with the cancer, transcription factors are upregulated or have higher expression.

    The findings suggest that cancer-specific methylation differences potentially evolve due to perturbation in the activity or expression of transcription factors. Similar changes in DNA methylation patterns were observed in precancerous polyps.

    “These studies highlight that the transcription factor expression changes and corresponding DNA methylation changes are early events during tumor development,” says lead study author Yuba Bhandari, Ph.D., a research associate at the Johns Hopkins Kimmel Cancer Center. “As polyps do not carry all of the key genetic changes typically found in full-blown cancer cells, the transcription factor changes may represent the earliest molecular regulators of precancerous cells, with profound impact on the genome-wide DNA methylation changes.”

    The specific set of transcription factors identified in the study may help in stratifying colorectal cancer prognosis, Easwaran adds.

    “This is particularly important, because multiple studies have shown that a certain subtype of colorectal cancers responds best to immune checkpoint blockade therapies, while others may not fare as well,” he says. “Expression profiling of relevant transcription factors may help develop better therapeutic strategies across subtypes of colorectal cancers.”

    Additional study co-authors included Rachael Powers, Sehej Parmar, Sara-Jayne Thursby, Ekta Gupta, Ozlem Kulak, Kurtis Bachman and Stephen Baylin of Johns Hopkins. Additional investigators from Janssen Research and Development in Pennsylvania and in Belgium contributed.

    The work was supported by the National Institutes of Health grants R01CA230995 and R01CA229240; National Institute of Environmental Health Sciences grant R01ES011858; National Cancer Institute grant R21CA212495; Sam Waxman Research Foundation and National Institute on Aging grant U01AG066101; Janssen Initiative; Commonwealth Grant; and Grollman Glick Scholarship.

    Baylin consults for MDxHealth. Methylation-specific PCR is licensed to MDxHealth in agreement with The Johns Hopkins University. Baylin and JHU are entitled to royalty shares received from sales. These arrangements have been reviewed and approved by The Johns Hopkins University in accordance with its conflict-of-interest policies.

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    Johns Hopkins Medicine

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  • 10 Quick Facts about Sarcoma, one of the Rarest Cancers

    10 Quick Facts about Sarcoma, one of the Rarest Cancers

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    Newswise — New Brunswick, N.J. July 1, 2023 – From the top of your head to your toes, sarcoma can grow in bones, muscles, tendons, cartilage, and any connective tissue, which makes it a difficult disease to detect. Understanding more about this disease can help people to identify it early. Adam C. Berger, MD, FACS, chief of Melanoma and Soft Tissue Surgical Oncology and associate director for Shared Resources at Rutgers Cancer Institute of New Jersey shares some facts.

    1. According to the American Cancer Society, sarcoma, often called ‘the forgotten cancer,’ makes up approximately 1 percent of all adult cancer diagnoses.
    2. There are two broad categories for sarcoma. The first category is soft tissue sarcoma, which means that the cancer arises in the soft tissue elements of anywhere in the body (extremity, chest, abdomen, etc), such as muscles, fat, nerves and blood vessels. The second category is bone sarcoma, which are cancers that originate in the bone.
    3. The most common areas sarcoma tumors grow are the legs, ands, arms, neck, chest, shoulders, abdomen, and hips.
    4. These are further classified into more than 70 sarcoma subtypes. Subtypes of sarcoma are named based on the surrounding tissue, the affected area of the bone or the type of cells creating the tumor.
    5. The most common types of sarcoma are soft tissue sarcomas, including angiosarcomas, fibrosarcomas, leiomyosarcomas, rhabdomyosarcomas, liposarcomas and synovial sarcomas.
    6. Osteosarcomas (bone sarcomas) are the second most common type, with the least frequent type being sarcomas that develop in internal organs, such as the lungs.
    7. The symptoms of sarcomas vary because they take multiple forms in multiple locations. For example, in their early stages, soft tissue sarcomas rarely display any symptoms other than a painless lump. As the tumor grows, pain may occur depending on where the tumor is located, or if it presses on nearby nerves.
    8. With sarcoma of the bone, pain is the most common symptom. Treatments for sarcomas are dependent upon the subtype a patient has and will vary widely depending on a variety of other factors such as tumor location and size, the patient’s age and if the tumor is new or recurrent.
    9. There are known inherited disorders, including Li-Fraumeni syndrome, that significantly increase the risk of developing both soft-tissue and bone sarcoma – particularly among children and young adults.
    10. Expertise is critical. With a rare and complex type of cancer such as sarcoma, it is important to seek the best possible care.

    Experts at Rutgers Cancer Institute, New Jersey’s only National Cancer Institute (NCI)-designated Comprehensive Cancer Center together with RWJBarnabas Health are involved in various precision medicine initiatives for sarcomas focusing on personalized treatment for metastatic disease as well as early detection. Clinical trials for sarcomas are also currently being conducted, focusing on both targeted therapy and immunotherapy for treatment of the disease. Learn more: https://www.cinj.org/patient-care/sarcoma-and-soft-tissue-oncology-program.

     

     

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    Rutgers Cancer Institute of New Jersey

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  • Blood test aids in predicting lung cancer mortality risk

    Blood test aids in predicting lung cancer mortality risk

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    Newswise — HOUSTON ― A blood-based test developed by researchers at The University of Texas MD Anderson Cancer Center can predict an individual’s risk of dying from lung cancer when combined with a personalized risk model.

    According to new data published today in the Journal of Clinical Oncology, a blood-based four-protein panel (4MP), when combined with a lung cancer risk model (PLCOm2012), can better identify those at high risk of dying from lung cancer than the current U.S. Preventive Services Task Force (USPSTF) criteria.

    These findings build upon previous MD Anderson research demonstrating the combination test more accurately determined who is likely to benefit from lung cancer screening than the USPSTF criteria.

    “This simple blood test has the potential to save lives by determining the need for lung cancer screening on a personalized basis,” said co-corresponding author Samir Hanash, M.D., Ph.D., professor of Clinical Cancer Prevention. “Given the challenges associated with CT as a frontline screening method for lung cancer and the fact that most individuals diagnosed with the disease do not meet current guidelines, there is an urgent demand for an alternative approach.”

    For this study, MD Anderson researchers analyzed pre-diagnostic blood samples from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, including 552 individuals who later developed lung cancer and 2,193 who did not. Of the 552 individuals diagnosed during the six-year study period, 70% (387) died from lung cancer.

    Using hazard ratios, the researchers assessed the relationship between the risk scores generated by the combination model (4MP + PLCOm2012) and the incidence of lung cancer death. The combination showed improved sensitivity, specificity and positive predictive value compared to the 2013 and 2021 USPSTF criteria for predicting lung cancer-specific mortality among individuals who smoked at least 10 pack-years (PYs).

    The USPSTF recommends that adults at elevated risk for lung cancer receive a low-dose CT scan each year, which was shown to reduce lung cancer deaths in the 2011 National Lung Screening Trial (NLST). The 2021 USPSTF criteria applies to adults aged 50 to 80 who have at least a 20 PY smoking history and currently smoke or have quit within the past 15 years.

    “For individuals who currently are not eligible for lung cancer screening, a positive test may help to identify those possibly at risk for lung cancer death,” said co-corresponding author Edwin Ostrin, M.D., Ph.D., assistant professor of General Internal Medicine. “We envision this as a tool that could be deployed worldwide, as the future of early detection of this disease.”

    Lung cancer causes an estimated 25% of cancer deaths. Early detection improves prospects of survival, but most countries do not screen for it. Fewer than half of all U.S. cases are among people who are eligible under USPSTF guidelines.

    While the blood test could be implemented as a lab-developed test in the near future, Food and Drug Administration (FDA) approval likely would require evaluation through a prospective clinical trial.

    Hanash is an inventor on a patent application related to the blood test. A complete list of co-authors and their disclosures is included in the paper.

    This study was supported by the National Institutes of Health and National Cancer Institute (U01CA194733, U01CA213285, U01CA200468, U24CA086368), the Cancer Prevention & Research Institute of Texas, Lyda Hill Philanthropies, and the Lung Cancer Moon Shot®, part of MD Anderson’s Moon Shots Program®.

    Read the full release on the MD Anderson Newsroom. 

     

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    University of Texas MD Anderson Cancer Center

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  • Treatment decisions in new era of individualized therapy for metastatic hormone-sensitive prostate cancer guided by Dana-Farber case study

    Treatment decisions in new era of individualized therapy for metastatic hormone-sensitive prostate cancer guided by Dana-Farber case study

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    RESEARCH SUMMARY

    Study Title: Early Treatment Intensification in Metastatic Hormone-Sensitive Prostate Cancer

    Publication: Journal of Clinical Oncology

    Dana-Farber Cancer Institute authors: Jeremiah Wala; MD, PhD, Paul Nguyen, MD, MBA; Mark Pomerantz, MD

    Summary: Oncologists have traditionally prescribed androgen deprivation therapy (ADT) alone for patients with metastatic hormone-sensitive prostate cancer (mHSPC).

    Newswise — Now there are many possible treatment options. Clinical trials have shown that more aggressive up-front treatment with a range of combination therapies improves outcomes. This case study shows how Dana-Farber Cancer Institute oncologists interpreted the evidence from these trials and applied it to an individual patient with mHSPC.

    The researchers recommend aggressive up-front treatment with triplet therapy (ADT, an androgen-receptor pathway inhibitor, and chemotherapy) for patients who can tolerate chemotherapy, and especially for patients with high-volume disease. For patients with low-volume disease, they recommend adding radiation therapy if feasible. The researchers also recommend the use of PSMA-PET scans to find metastases, evaluate treatment response, and identify potential sites for radiation.

    Impact: Choosing a treatment approach requires interpretation of the results of many trials and the consideration of multiple factors unique to each patient. This case study provides that interpretation and gives evidence-based guidance for how to navigate decision-making for individual patients. 

    Funding: This study was funded by the National Cancer Institute. 

    # # #

     

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    Dana-Farber Cancer Institute

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  • Pan-cancer T cell atlas reveals new details of tumor microenvironment

    Pan-cancer T cell atlas reveals new details of tumor microenvironment

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    Newswise — HOUSTON ― A new study led by researchers at The University of Texas MD Anderson Cancer Center, published today in Nature Medicine, provides a deeper understanding of the vast diversity of T cell states as well as their relationships and roles within the complex tumor microenvironment, bringing a fresh perspective to understanding immunotherapy efficacy in cancer.

    Recent studies have shown that the phenotypic states of T cells, as well as their relative proportions, play a crucial role in determining the effectiveness of immunotherapy and the likelihood of potential adverse effects. This new pan-cancer single-cell T cell atlas integrates 27 single-cell RNA sequencing datasets, including nine unique datasets from MD Anderson, covering 16 cancer types. It is the most detailed picture to date of the heterogeneity of T cells present within the tumor microenvironment.

    “This kind of large dataset and comprehensive pan-cancer analysis provides the opportunity to see things that aren’t visible when studying a single type of cancer or even a handful of cancer types,” said corresponding author Linghua Wang, M.D., Ph.D. associate professor of Genomic Medicine. “We hope these high-resolution maps, including the thoroughly characterized T cell states, are valuable resources for facilitating future T cell studies and biomarker discovery.”

    One notable discovery from this study is the previously undescribed T cell stress response state, or TSTR. In prior single-cell studies, these T cells often were overlooked or considered to be artifacts related to tissue dissociation. However, with the extensive data available, the researchers were able to identify these cells as a clearly unique group, distinct from other CD4+ or CD8+ T cell subsets, and to validate their existence in situ using multiple spatial profiling methods.

    TSTR cells can be thought of as ‘stressed out’ T cells and, just like a stressed person might be less effective at their job, they seem to be less effective at fighting cancer. While both TSTR cells and exhausted T cells may be dysfunctional, TSTR cells appear to follow a unique differentiation path, distinct from the trajectory of exhausted T cells.

    TSTR cells are characterized by high heat shock gene expression and, importantly, are seen at significantly higher fractions in both CD4+ and CD8+ T cells following immune checkpoint blockade therapy, particularly in non-responders. This suggests TSTR cells may play a role in resistance to immunotherapy. This new T cell state adds an additional layer to our understanding of the intricate biology of cancer and provides a potential target for future therapies.

    “The fact that these TSTR cells are found in many different types of tumors opens up a whole new world of possibilities that could have high translational potential,” Wang said. “Investigating the mechanistic causes of stress response in T cells, understanding how these stressed T cells are induced in the tumor microenvironment, and learning how to stop or reverse this TSTR state could catalyze the development of more effective therapeutic strategies that may bring the benefit of immunotherapy to more cancer patients.”

    This work also underscores the value of large, integrative datasets in oncology. This pan-cancer T cell atlas exemplifies the power of big data to unravel the complex landscape of T cells within tumors. The researchers described a total of 32 T cell states in this study, and further identified seven subpopulations within the CD4+ regulatory subset, five within the CD4+ follicular helper T cell population, and eight states among proliferating T cells.

    These findings all highlight the extensive heterogeneity of T cell states within the tumor microenvironment and the need to further understand how these states contribute to disease progression and immunotherapy response.

    “There are still many questions left to answer,” Wang said. “One of the limitations of this study is we don’t have the corresponding T cell receptor data for most of the datasets analyzed. We are not sure what triggers the TSTR state, and we don’t know from which T cell subset(s) they originate. It also is unclear whether these TSTR cells are specific to tumor cells and how they communicate with and influence other cells within the tumor microenvironment.”

    The research team has shared their T cell atlas with the wider research community through the Single-Cell Research Portal, a user-friendly, interactive web portal. This portal, developed by the team, allows both internal and external users to visualize and query the atlas without the need for bioinformatics skills.

    The team has also developed a tool named TCellMap, which enables researchers to automatically annotate T cells from their datasets by aligning with the high-resolution T cell maps generated by this study. Wang expressed her hope that these resources will prove valuable to scientists aiming to perform an in-depth analysis of T cells, leading to further discoveries and ultimately enhancing strategies for T cell therapy.

    Dr. Yanshuo Chu, Ph.D., from the Wang laboratory led the data analysis. This research was supported by MD Anderson, the National Institutes of Health/National Cancer Institute (R01CA266280, U01CA264583, P50CA016672, T32CA217789), the Cancer Prevention and Research Institute of Texas (CPRIT) and the U.S. Department of Defense. A full list of collaborating authors and their disclosures can be found with the full paper here.

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    University of Texas MD Anderson Cancer Center

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  • Red flags indicate risk for early-onset colorectal cancer

    Red flags indicate risk for early-onset colorectal cancer

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    Newswise — Researchers at Washington University School of Medicine in St. Louis have identified four important signs and symptoms that signal an elevated risk of early-onset colorectal cancer. These red flags may be key to earlier detection and diagnosis of early-onset colorectal cancer among younger adults. The number of young adults with colorectal cancer has nearly doubled in recent years.

    Studying de-identified health insurance data on more than 5,000 patients with early-onset colorectal cancer — cancer that occurs before a person turns 50 — the researchers found that in the period between three months and two years before diagnosis, abdominal pain, rectal bleeding, diarrhea and iron deficiency anemia each indicate an increased risk in those under age 50. They found that having a single one of the symptoms almost doubled the risk; having two symptoms increased risk by more than 3.5 times; and having three or more boosted the risk by more than 6.5 times.

    The study is published May 4 in the Journal of the National Cancer Institute.

    “Colorectal cancer is not simply a disease affecting older people; we want younger adults to be aware of and act on these potentially very telling signs and symptoms — particularly because people under 50 are considered to be at low risk, and they don’t receive routine colorectal cancer screening,” said senior investigator Yin Cao, ScD, an associate professor of surgery in the Public Health Sciences Division, and a research member of Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine.

    “It’s also crucial to spread awareness among primary care doctors, gastroenterologists and emergency medicine doctors,” Cao said. “To date, many early-onset colorectal cancers are detected in emergency rooms, and there often are significant diagnostic delays with this cancer.”

    Cao said two symptoms in particular — rectal bleeding and iron deficiency anemia, a condition in which there are not enough healthy red blood cells to carry oxygen — point to the need for timely endoscopy and follow-up.

    In this study, Cao, with first author Cassandra D. L. Fritz, MD, an assistant professor of medicine in the Division of Gastroenterology, and co-first author Ebunoluwa Otegbeye, MD, a general surgery resident, analyzed cases of early-onset colorectal cancer and matched controls using the IBM MarketScan Commercial Database, a big-data tool that provides longitudinal, de-identified information based on health insurance claims data from about 113 million insured adults ages 18 to 64.

    “It usually takes about three months to get a diagnosis from the time a person first goes to the doctor with one or more of the red-flag signs and symptoms we’ve identified,” Fritz said. “But in this analysis, we found that some young adults had symptoms for up to two years prior to their diagnoses. That may be part of the reason many of these younger patients had more advanced disease at the time of diagnosis than what we normally see in older people who get screened regularly.”

    Individuals born in 1990 have double the risk of colon cancer and four times the risk of rectal cancer compared with young adults born in 1950. That trend has prompted the National Cancer Institute, American Cancer Society, American Gastroenterological Association and other professional societies to prioritize research on identifying risk factors and improving early detection. In 2021, the U.S. Preventive Services Task Force lowered the recommended age for colorectal cancer screening from 50 to 45.

    Cao, also an associate professor of medicine, leads a research group focused on identifying risk factors and molecular variations in early-onset colorectal cancer. Her group is among the first to report that obesity, prolonged sitting, metabolic syndrome, diabetes, sugar-sweetened beverages and other risk factors may contribute to the rising incidence of early-onset colorectal cancer.

    According to the American Cancer Society, although the death rate from colorectal cancer has been dropping for several decades in older adults due to regular colonoscopies and improved treatment, more younger people are diagnosed with the disease at advanced stages, and many are dying of the disease.

    Such a shift suggests urgency in recognizing symptoms as early as possible.

    “Since the majority of early-onset colorectal cancer cases have been and will continue to be diagnosed after symptom presentation, it is crucial to recognize these red-flag signs and symptoms promptly and conduct a diagnostic work-up as soon as possible,” Cao said. “By doing so, we can diagnose the disease earlier, which in turn can reduce the need for more aggressive treatment and improve patients’ quality of life and survival rates.”

    Fritz, CDL. Otegbeye EE, Zong X, Demb J, Nickel KB, Olsen MA, Mutch M, Davidson NO, Gupta S, Cao Y. Red-flag signs and symptoms for earlier diagnosis of early-onset colorectal cancer. The Journal of the National Cancer Institute, May 4, 2023.

    The study was funded with support from the National Center for Advancing Translational Sciences, the National Cancer Institute and the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health (NIH). Grant numbers: UL1 TR002345, T32 DK007130, T32 CA009621, P30 DK52574 and R37 CA246175.

    About Washington University School of Medicine

    WashU Medicine is a global leader in academic medicine, including biomedical research, patient care and educational programs with 2,800 faculty. Its National Institutes of Health (NIH) research funding portfolio is the third largest among U.S. medical schools, has grown 52% in the last six years, and, together with institutional investment, WashU Medicine commits well over $1 billion annually to basic and clinical research innovation and training. Its faculty practice is consistently within the top five in the country, with more than 1,800 faculty physicians practicing at 65 locations and who are also the medical staffs of Barnes-Jewish and St. Louis Children’s hospitals of BJC HealthCare. WashU Medicine has a storied history in MD/PhD training, recently dedicated $100 million to scholarships and curriculum renewal for its medical students, and is home to top-notch training programs in every medical subspecialty as well as physical therapy, occupational therapy, and audiology and communications sciences.

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    Washington University in St. Louis

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  • Connecticut Magazine’s 2023 “Top Doctors” issue recognizes 82 Smilow Cancer Hospital and Yale Cancer Center physicians

    Connecticut Magazine’s 2023 “Top Doctors” issue recognizes 82 Smilow Cancer Hospital and Yale Cancer Center physicians

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    Newswise — Each year, Connecticut Magazine recognizes some of the state’s best physicians, who provide exceptional care for patients, with its annual “Top Doctors” issue. This year’s list includes 82 physicians from Smilow Cancer Hospital and Yale Cancer Center, the only National Cancer Institute-designated comprehensive cancer center in the state.

    “It is wonderful for many of us to be included on the 2023 list of top cancer doctors in Connecticut,” said Eric Winer, MD, director of Yale Cancer Center and physician-in-chief of Smilow. “This is a top honor, and we are grateful for the recognition and the support.”

    The magazine partnered with Castle Connolly, a leading national health care research firm, to compile the annual list of the state’s top physicians. Castle Connolly’s extensive survey identified more than 1,600 Connecticut physicians, all nominated by their peers and vetted to meet the criteria to earn the designation of “Top Doctors.” In other words, these are the cancer experts who other doctors recommend. The complete “Top Doctors” list appears in the May 2023 issue of Connecticut Magazine.

    Congratulations to this year’s “Top Doctors” affiliated with Smilow Cancer Hospital and Yale Cancer Center:

     

    Top Doctors

    Nita Ahuja — Surgery

    Michael Alperovich — Surgery

    Harry Aslanian — Gastroenterology

    Masoud Azodi — Gynecologic Oncology

    Joachim Baehring — Neurology

    Elizabeth Berger — Breast Surgical Oncology

    Jean Bolognia — Dermatology

    Robert Bona — Hematology & Oncology

    D. Barry Boyd — Medical Oncology

    James Clune — Surgery

    Michael Cohenuram — Thoracic Oncology

    John Colberg — Urology

    Frank Detterbeck — Thoracic Surgery

    Kevin Du — Therapeutic Radiology

    Andrew Duffy — Surgery

    Beverly Drucker — Medical Oncology

    Richard Edelson — Dermatology

    Neal Fischbach — Medical Oncology

    Francine Foss — Medical Oncology-Hematology-Oncology

    Gary Frielaender —Pathology-Musculoskeletal Oncology

    Scott Gettinger — Thoracic Oncology-Medical Oncology

    Michael Girardi — Dermatology

    Earl Glusac — Pathology-Dermatology

    Rachel Greenup — Breast Surgical Oncology

    Roy Herbst — Medical Oncology-Thoracic Oncology

    Susan Higgins — Therapeutic Radiology-Breast Cancer Radiotherapy

    Silvio Inzucchi —Endocrinology-Diabetes Medicine & Management

    Gary Israel — Radiology-Biomedical Imaging

    Dhanpat Jain — Pathology-Internal Medicine (Digestive Diseases)

    Priya Jamidar — Gastroenterology-Hepatology

    Michele Johnson — Radiology-Biomedical Imaging

    Kimberly Johung — Therapeutic Radiology

    Benjamin Judson — Surgery

    Jennifer Kapo — Internal Medicine-Hospice & Palliative Care

    Patrick Kenney — Urology

    Sajid Khan — Surgical Oncology-Gastrointestinal Surgery

    Sanjay Kulkarni — Surgery

    Pamela Kunz — Medical Oncology

    Jill Lacy — Medical Oncology

    Johanna LaSala — Medical Oncology-Hematology & Oncology

    Stephen Lattanzi — Medical Oncology

    Alfred Lee — Hematology

    Merlin Lee (M.Sung Lee) — Hematology-Oncology 

    David Lefell — Dermatology

    Jonathan Leventhal ­­— Dermatology

    Walter Longo — Surgery

    Maryam Lustberg — Breast Oncology 

    David Madoff — Radiology-Biomedical Imaging 

    Asher Marks — Pediatric Hematology & Oncology 

    Kelsey Martin — Hematology & Oncology 

    Bruce McGibbon —Therapeutic Radiology 

    Saral Mehra — Surgery

    Ehud Mendel — Neurosurgery 

    Jon Morrow — Pathology 

    David Mulligan — Surgery 

    Justin Persico — Medical Oncology 

    Daniel Petrylak — Medical Oncology-Urology 

    Jeffrey Pollak — Radiology-Biomedical Imaging 

    Jennifer Possick — Thoracic Oncology

    Lajos Pusztai — Medical Oncology, Breast Oncology

    Elena Ratner — Gynecologic Oncology 

    Vikram Reddy — Colon and Rectal Surgery

    David Rimm — Pathology-Medical Oncology

    Kenneth Roberts — Therapeutic Radiology-Medical Oncology

    Alessandro Santin — Gynecologic Oncology

    Ronald Salem — Surgery

    Niketa Shah — Hematology & Oncology

    Sangini Sheth — Gynecologic Oncology

    Dinish Singh — Urology

    Kathleen Suozzi — Dermatology

    Gordon Sze — Radiology-Biomedical Imaging

    Mario Sznol — Medical Oncology 

    Lynn Tanoue — Pulmonology & Sleep Medicine

    Kelsey Martin Thompson — Hematology

    Hugh Taylor — Gynecologic Oncology

    Juan Vasquez — Pediatric Hematology-Oncology

    Jeffrey Weinreb — Radiology-Biomedical Imaging

    Lynn Wilson — Therapeutic Radiology

    Eric Winer — Medical Oncology

    David Witt — Medical Oncology

    George Yavorek — Colorectal Surgery

    Nwanmegha Young — Clinical Surgery

    *Alex Choi in the Palliative Care Program at Smilow Cancer Hospital was also named a 2023 Castle Connolly Rising Star

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  • Study Finds Relationship Between Discrimination and Frailty in Black Cancer Survivors

    Study Finds Relationship Between Discrimination and Frailty in Black Cancer Survivors

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    Newswise — WASHINGTON — Discrimination experienced by Black people can affect their health and increase their frailty, which can be particularly impactful for cancer survivors, according to a new study by researchers at Georgetown University’s Lombardi Comprehensive Cancer Center and colleagues at the Barbara Ann Karmanos Cancer Institute in Detroit. The researchers assessed frailty by a number of factors, including whether a participant had several chronic diseases, poor muscle strength and difficulty performing activities of daily living.

    The findings appeared March 20, 2023, in Cancer.

    “Discrimination can act as a chronic stressor which can throw the body off balance, resulting in increases in blood pressure, heart rate, metabolism, inflammation, and numerous other factors. These stressors can also increase rates of aging, leading to greater risk of frailty,” says the study’s lead investigator, Jeanne Mandelblatt, MD, MPH, director of the Georgetown Lombardi Institute for Cancer and Aging Research. “We hypothesize that discrimination can lead to an older biological age than a person’s actual chronological age. This is important to understand as there have been virtually no studies of the relationships between discrimination and aging in the setting of cancer survivorship.”

    The investigators looked at associations between discrimination and frailty among 2,232 Black breast, lung, prostate and colorectal cancer survivors who were within five years of their diagnoses and were no longer actively being treated for their cancers. Survivors were 62 years of age on average (with ages ranging from 23 to 84) at the time of the study, but they may have experienced discrimination over many decades of their lives. All participants were part of the Detroit Research on Cancer Survivors (ROCS), which is the largest U.S. study of Black cancer survivors.

    The researchers surveyed the participants, via phone, in writing, or online about any aging-related diseases they had, their ability to maintain a healthy lifestyle, and most importantly, about major discrimination events they may have experienced over their lifetimes, specifically targeting seven areas:

    • being unfairly fired or denied a promotion in their job;
    • not being hired for a job;
    • being unfairly stopped, searched, questioned, physically threatened or abused by police officers;
    • being unfairly discouraged by a teacher or advisor from continuing their education;
    • unfairly receiving worse medical care than other people;
    • being prevented from moving into a neighborhood because a landlord or realtor refused to sell or rent them a house or an apartment; and/or
    • moved into a neighborhood where neighbors made life difficult.

    Based on the survey results, the majority of cancer survivors were classified as either prefrail (42.7%), meaning they had some health difficulties, or frail (32.9%). Only 24.4% of those surveyed had few or no signs of frailty. When queried about the seven discrimination areas, 63.2% of the participants reported experiencing major discrimination, with an average respondent reporting 2.4 types of discrimination.

    “For those cancer survivors who reported four to seven types of discrimination events, we observed a large, clinically meaningful increase in frailty scores compared to survivors with fewer discrimination events,” explains Mandelblatt, also a professor of oncology and medicine at the Georgetown University School of Medicine. “Significantly, this pattern of discrimination affecting frailty was consistent across the four types of cancer surveyed, indicating that discrimination is an important factor to study and understand in Black cancer survivors in order to improve their quality and length of life.”

    “Our results indicate that after considering the effects of traditional factors on poor health, such as income, education and types of cancer treatment, discrimination was a significant factor explaining frailty and it acted independently of the other variables,” says  Ann Schwartz, PhD, MPH, co-lead author on the paper and co-principal investigator of the Detroit ROCS. “Regardless of whether you were rich or poor, if you experienced more discrimination then you had greater frailty.” Schwartz is also professor and associate chair of oncology at Wayne State University School of Medicine, and deputy center director and executive vice president for research and academic affairs at Karmanos.

    For their next steps, the researchers are hoping to study the relationships between major discrimination, other chronic life stressors and markers of biological aging and test how cancer and its treatment further contributes to biological aging among racial and ethnic minorities. 

    “We have long since recognized the impact of discrimination on health and well-being in Black communities,” says study co-author Lucile Adams-Campbell, PhD, a professor of oncology and associate director for Minority Health and Health Disparities Research at Georgetown Lombardi. “We hope that this study leads to more discussions between providers and their patients about the types of discrimination they have experienced and gives providers a greater understanding of how discrimination impacts frailty.”

                                                                ###

    Additional authors include Xingtao Zhou and Traci Bethea at Georgetown Lombardi; Julie Ruterbusch, Hayley Thompson and Kristen Purrington at Wayne State University School of Medicine and Karmanos Cancer Institute.

    The authors report having no personal financial interests related to the study.

    This research was supported by National Cancer Institute grants U01 CA199240, R01CA129769,  R35CA197289 and K01CA212056 and a National Institute on Aging grant R21AG07500. This work was supported by the Epidemiology Research Core and the National Cancer Institute Center Grant (P30CA022453) awarded to the Karmanos Cancer Institute at Wayne State University.

    About Georgetown University’s Lombardi Comprehensive Cancer Center
    Georgetown’s Lombardi Comprehensive Cancer Center is designated by the National Cancer Institute (NCI) as a comprehensive cancer center. A part of Georgetown University Medical Center, Georgetown Lombardi is the only comprehensive cancer center in the Washington D.C. area. It serves as the research engine for MedStar Health, Georgetown University’s clinical partner. Georgetown Lombardi is also an NCI recognized consortium with John Theurer Cancer Center/Hackensack Meridian Health in Bergen County, New Jersey. The consortium reflects an integrated cancer research enterprise with scientists and physician-researchers from both locations. Georgetown Lombardi seeks to improve the diagnosis, treatment, and prevention of cancer through innovative basic, translational and clinical research, patient care, community education and outreach to service communities throughout the Washington region, while its consortium member John Theurer Cancer Center/Hackensack Meridian Health serves communities in northern New Jersey. Georgetown Lombardi is a member of the NCI Community Oncology Research Program (UG1CA239758). Georgetown Lombardi is supported in part by a National Cancer Institute Cancer Center Support Grant (P30CA051008). Connect with Georgetown Lombardi on Facebook (Facebook.com/GeorgetownLombardi) and Twitter (@LombardiCancer).

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  • Can ChatGPT be Counted On?

    Can ChatGPT be Counted On?

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    Newswise — A study in the Journal of The National Cancer Institute Cancer Spectrum looked at chatbots and artificial intelligence (AI), as they become popular resources for cancer information. They found these resources give accurate information when asked about common cancer myths and misconceptions. In the first study of its kind, Skyler Johnson, MD, physician-scientist at Huntsman Cancer Institute and assistant professor in the department of radiation oncology at the University of Utah (the U), evaluated the reliability and accuracy of ChatGPT’s cancer information.

    Using the National Cancer Institute’s (NCI) common myths and misconceptions about cancer, Johnson and his team found that 97% of the answers were correct. However, this finding comes with some important caveats, including a concern amongst the team that some of the ChatGPT answers could be interpreted incorrectly. “This could lead to some bad decisions by cancer patients. The team suggested caution when advising patients about whether they should use chatbots for information about cancer,” says Johnson.

    The study found reviewers were blinded, meaning they didn’t know whether the answers came from the chatbot or the NCI. Though the answers were accurate, reviewers found ChatGPT’s language was indirect, vague, and in some cases, unclear.

    “I recognize and understand how difficult it can feel for cancer patients and caregivers to access accurate information,” says Johnson. “These sources need to be studied so that we can help cancer patients navigate the murky waters that exist in the online information environment as they try to seek answers about their diagnoses.”

    Incorrect information can harm cancer patients. In a previous study by Johnson and his team published in the Journal of the National Cancer Institute, they found that misinformation was common on social media and had the potential to harm cancer patients.

    The next steps are to evaluate how often patients are using chatbots to seek out information about cancer, what questions they are asking, and whether AI chatbots provide accurate answers to  uncommon or unusual questions about cancer.

    The study was supported by the National Institutes of Health/National Cancer Institute including P30 CA042014 and Huntsman Cancer Foundation.

    About Huntsman Cancer Institute at the University of Utah

    Huntsman Cancer Institute at the U is the official cancer center of Utah and the only National Cancer Institute-designated Comprehensive Cancer Center in the Mountain West. The campus includes a state-of-the-art cancer specialty hospital and two buildings dedicated to cancer research. Huntsman Cancer Institute provides patient care, cancer screening, and education at community clinics and affiliate hospitals throughout the Mountain West. It is consistently recognized among the best cancer hospitals in the country by U.S. News and World Report. The region’s first proton therapy center opened in 2021 and a major hospital expansion is underway. Huntsman Cancer Institute is committed to creating a diverse and inclusive environment for staff, students, patients, and communities. Advancing cancer research discoveries and treatments to meet the needs of patients who live far away from a major medical center is a unique focus. More genes for inherited cancers have been discovered at Huntsman Cancer Institute than at any other cancer center, including genes responsible for breast, ovarian, colon, head and neck cancers, and melanoma. Huntsman Cancer Institute was founded by Jon M. and Karen Huntsman.

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  • Microcalcification ‘fingerprints’ can yield info about cancer

    Microcalcification ‘fingerprints’ can yield info about cancer

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    Newswise — ITHACA, N.Y. — An interdisciplinary collaboration 10 years in the making used a materials science approach to “fingerprint” the calcium mineral deposits known as microcalcifications that reveal pathological clues to the progression of breast cancer and potentially other diseases.

    The group’s paper, “Biomineralogical Signatures of Breast Microcalcifications,” published Feb. 22 in Science Advances. The lead author is postdoctoral researcher Jennie Kunitake, Ph.D. ’21.

    Healthy mineral deposition is a delicately orchestrated process, as seen in bone and tooth formation. Sometimes, however, mineral deposits form in places they don’t belong, such as kidneys – i.e., kidney stones – and breast tissue. In the context of breast cancer, microcalcifications are a critical screening tool because they appear as vivid white specks in mammograms and, in certain cases, indicate the presence of breast cancer.

    “Usually after the initial mammogram, microcalcifications are largely ignored. And what we’re saying is we can look beyond the resolution of the mammogram, at the microscopic and chemical level, and get more information from these microcalcifications,” said co-senior author Lara Estroff, professor of materials science and engineering in Cornell Engineering. “By taking well-established, high-resolution characterization techniques from materials science and coupling those with an appreciation for biomineralization and how organisms can control the deposition of mineral, we’ve gained a unique insight into a pathological mineral that may have important implications for disease.”

    Estroff’s group specializes in biomineralization, i.e., how biological organisms control the growth of crystals in their tissues. More than a decade ago, she began collaborating with Claudia Fischbach, the Stanley Bryer 1946 Professor of Biomedical Engineering and a co-senior author of the paper, to explore the metastatic spread of breast cancer to bone. This led to an exploration of a “bizarre” phenomenon in which bone-like mineral appeared at primary tumor sites, and from there the collaborators became interested in the ways these microcalcifications can capture elements of the tissue microenvironment where they form, almost like a snapshot. The microenvironment, also known as the organic matrix, can in turn influence the mineral’s composition, morphologies and mechanical properties.

    “Minerals have different rules than biology,” Kunitake said. “Minerals forming in breast cancer could be trapping chemical information that reflect their formation environment, and that could potentially have clinical value and relevance.”

    While some cancer biologists have studied microcalcifications, the phenomenon has not been explored by materials scientists.

    “Biomineralization is a rather niche area that involves contributions from materials science, geology, biology and more. It’s very multidisciplinary,” Estroff said. “There’s absolutely no reason that oncologists would pay attention to the materials properties of these tiny little crystals that are appearing. I think it really took someone who had an idea of what the mineral could be offering to do this. We said, can we take everything that we know from studying physiological biominerals, and apply it now to these pathological minerals?”

    Fischbach connected Estroff and Kunitake with researchers at Memorial Sloan Kettering Cancer Center, who provided tissue samples containing microcalcifications from 40 breast cancer patients.

    Kunitake then began the arduous, years-long process of trying to understand exactly what they were looking at. She turned to Dr. Daniel Sudilovsky, then at Cayuga Medical Center, who helped characterize the pathology of each type of microcalcification they found.

    Next, rather than grind up and homogenize the tissue samples, as other studies had done, the researchers sought to obtain high-resolution, three-dimensional maps of the chemistry of the mineral and the organic matrix, such that they wouldn’t alter the tissue structure. So they collaborated with Admir Masic of Massachusetts Institute of Technology, a co-senior author of the paper, who used a vibrational spectroscopy technique called Raman microscopy that can detect the distinct vibrational signatures of a biological molecule’s organic and inorganic chemistries, and also map where those signatures are occurring.

    Kunitake then set about integrating and parsing all the data using techniques that were inspired by omics research in biochemistry and genetics.

    “One way to look at data, when you have a lot of it, is to use strategies from the omics communities,” Kunitake said. “It doesn’t have to be quantitative, just to visualize how the data behaves. Using hierarchical clustering, we could look at our data as a heatmap, and that gave us an idea of how different parameters that we measured were related to one another, and how the different calcifications grouped based on their fingerprints.”

    Among the researchers’ key findings: cancer-associated microcalcifications cluster into physiologically relevant groups that reflect the tissue type and local malignancy; mineral carbonate exhibits substantial variety inside the tumor; trace metals – including zinc, iron and aluminum – are enhanced in malignant-localized calcifications; and the ratio of lipids to proteins within microcalcifications is lower in patients with poor prognosis.

    While the researchers are not sure if the microcalcifications form before the cancer develops or because of it, the findings indicate there is a correlation with disease severity. The researchers are hopeful the findings may also illuminate calcifications in other types of cancer, such as thyroid and ovarian cancer.

    The team now plans to study a larger spread of disease characteristics, and also apply their approach to other pathological mineralization diseases, such as calcific aortic valve disease, in which mineral forms in the heart valve, or as Estroff says, “the mineral is the disease.”

    Co-authors include: Lynn Johnson, director and statistical consultant of the Cornell Statistical Consulting Unit; postdoctoral researcher Siyoung Choi; Dr. Daniel Sudilovsky of Kingman Regional Medical Center in Kingman, Arizona; Dr. Neil Iyengar, a medical oncologist in the Breast Medicine Service at Memorial Sloan Kettering Cancer Center and associate professor of medicine at Weill Cornell Medicine; and researchers from Memorial Sloan Kettering Cancer Center and MIT.

    The research was supported by the Human Frontier Science Program and by the National Cancer Institute’s Center on the Physics of Cancer Metabolism.

    The researchers made use of the Cornell Center for Materials Research, which is supported by the National Science Foundation’s MRSEC program, and the College of Veterinary Medicine’s Animal Health Diagnostic Center.

    -30-

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    Cornell University

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  • CHOP Researchers Develop New, More Accurate Computational Tool for Long-Read RNA Sequencing

    CHOP Researchers Develop New, More Accurate Computational Tool for Long-Read RNA Sequencing

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    Newswise — Philadelphia, January 20, 2023—On the journey from gene to protein, a nascent RNA molecule can be cut and joined, or spliced, in different ways before being translated into a protein. This process, known as alternative splicing, allows a single gene to encode several different proteins. Alternative splicing occurs in many biological processes, like when stem cells mature into tissue-specific cells. In the context of disease, however, alternative splicing can be dysregulated. Therefore, it is important to examine the transcriptome – that is, all the RNA molecules that might stem from genes – to understand the root cause of a condition.

    However, historically it has been difficult to “read” RNA molecules in their entirety because they are usually thousands of bases long. Instead, researchers have relied on so-called short-read RNA sequencing, which breaks RNA molecules and sequence them in much shorter pieces – somewhere between 200 to 600 bases, depending on the platform and protocol. Computer programs are then used to reconstruct the full sequences of RNA molecules. Short-read RNA sequencing can give highly accurate sequencing data, with a low per-base error rate of approximately 0.1% (meaning one base is incorrectly determined for every 1,000 bases sequenced). Nevertheless, it is limited in the information that it can provide due to the short length of the sequencing reads. In many ways, short-read RNA sequencing is like breaking a large picture into many jigsaw pieces that are all the same shape and size and then trying to piece the picture back together.

    Recently, “long-read” platforms that can sequence RNA molecules over 10,000 bases in length end-to-end have become available. These platforms do not require RNA molecules to be broken up before they are sequenced, but they have a much higher per-base error rate, typically between 5% to 20%. This well-known limitation has severely hampered the widespread adoption of long-read RNA sequencing. In particular, the high error rate has made it difficult to determine the validity of novel, previously unknown RNA molecules discovered in a particular condition or disease.

    To circumvent this problem, researchers at Children’s Hospital of Philadelphia (CHOP) have developed a new computational tool that can more accurately discover and quantify RNA molecules from these error-prone long-read RNA sequencing data. The tool, called ESPRESSO (Error Statistics PRomoted Evaluator of Splice Site Options), was reported today in Science Advances.

    “Long-read RNA sequencing is a powerful technology that will allow us to uncover RNA variation in rare genetic diseases and other conditions, like cancer,” said Yi Xing, PhD, director of the Center for Computational and Genomic Medicine at CHOP and senior author of the study. “We are probably at an inflection point in how we discover and analyze RNA molecules. The transition from short-read to long-read RNA sequencing represents an exciting technological transformation, and computational tools that reliably interpret long-read RNA sequencing data are urgently needed.”

    ESPRESSO can accurately discover and quantify different RNA molecules from the same gene – known as RNA isoforms – using error-prone long-read RNA sequencing data alone. To do so, the computational tool compares all long RNA sequencing reads of a given gene to its corresponding genomic DNA, and then uses the error patterns of individual long reads to confidently identify splice junctions – places where the nascent RNA molecule has been cut and joined – as well as their corresponding full-length RNA isoforms. By finding areas of perfect matches between long RNA sequencing reads and genomic DNA, as well as borrowing information across all long RNA sequencing reads of a gene, the tool is able to identify highly reliable splice junctions and RNA isoforms, including those that have not been previously documented in existing databases. 

    The researchers evaluated the performance of ESPRESSO using simulated data and data on real biological samples. They found that ESPRESSO performs better than multiple currently available tools, both in terms of discovering RNA isoforms and quantifying them. The researchers also generated and analyzed over 1 billion long RNA sequencing reads covering 30 human tissue types and three human cell lines, providing a useful resource for studying human transcriptome variation at the resolution of full-length RNA isoforms. 

    “ESPRESSO addresses a long-standing problem of long-read RNA sequencing and could usher in new opportunities of discovery,” Dr. Xing said. “We envision that ESPRESSO will be a useful tool for researchers to explore the RNA repertoire of cells in various biomedical and clinical settings.”

    This work was supported in part by the Immuno-Oncology Translational Network (IOTN) of the National Cancer Institute’s Cancer Moonshot Initiative (U01CA233074), other National Institutes of Health funding (R01GM088342, R01GM121827, and R56HG012310), along with a National Institutes of Health T32 Training Grant in Computational Genomics (T32HG000046). 

    Gao et al. “ESPRESSO: Robust discovery and quantification of transcript isoforms from error-prone long-read RNA-seq data,” Science Advances, January 20, 2023, DOI: 10.1126/sciadv.abq5072

    #

    About Children’s Hospital of Philadelphia: A non-profit, charitable organization, Children’s Hospital of Philadelphia was founded in 1855 as the nation’s first pediatric hospital. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals, and pioneering major research initiatives, the 595-bed hospital has fostered many discoveries that have benefited children worldwide. Its pediatric research program is among the largest in the country. The institution has a well-established history of providing advanced pediatric care close to home through its CHOP Care Network, which includes more than 50 primary care practices, specialty care and surgical centers, urgent care centers, and community hospital alliances throughout Pennsylvania and New Jersey, as well as a new inpatient hospital with a dedicated pediatric emergency department in King of Prussia. In addition, its unique family-centered care and public service programs have brought Children’s Hospital of Philadelphia recognition as a leading advocate for children and adolescents. For more information, visit http://www.chop.edu.

     

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  • Sanford Burnham Prebys researchers team up to discover potential pancreatic cancer drugs

    Sanford Burnham Prebys researchers team up to discover potential pancreatic cancer drugs

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    Newswise — LA JOLLA, CALIF. – Jan 05, 2023 – Cosimo Commisso, Ph.D., and Susanne Heynen-Genel, Ph.D., have received a grant from the National Cancer Institute (NCI) to advance a new treatment approach for pancreatic cancer. The four-year, $X project will identify potential drugs that can manipulate the pH of cells to stop pancreatic tumors from growing. The promising approach would selectively kill pancreatic cancer cells without affecting surrounding healthy cells.

    “Pancreatic cancer is a growing global health crisis, and there is an urgent need for better ways to treat it,” says Commisso, an associate professor at Sanford Burnham Prebys. “This project will help us find molecules that are the starting points to create new medicines.”

    Pancreatic cancer accounts for just 3% of cancer cases in the United States, but it is so difficult to treat that it is projected to become the second-leading cause of cancer-related death by 2030. According to the NCI, about 49,830 people died from pancreatic cancer in the United States in 2022.

    “Pancreatic cancer tends to be diagnosed late, because it’s an organ lying deep in the body and can grow undetected for years,” says Commisso. “Since I started working in this field more than a decade ago, we’ve managed to double the survival rates for people with pancreatic cancer. But that’s not good enough—the five-year survival rate after diagnosis is only around 10%.”

    Commisso and his team discovered that pancreatic cancer cells have a unique way of regulating their pH—a measure of acidity. Cells need to maintain a pH within a certain range to survive and grow. Pancreatic cancer cells control their pH by packaging up excess acid and storing it separately from the rest of the cell’s fluids. This process doesn’t occur in healthy cells.

    “One really promising aspect of this approach is that once we find the right drug, we’ll be able to kill the cancer cells without causing any damage to the rest of the body,” says Commisso.

    “Metabolic approaches like this are the future of targeted cancer therapy.”
    Transforming Commisso’s discoveries into a real medicine will require the drug discovery capabilities of Heynen-Genel and her team at the Conrad Prebys Center for Chemical Genomics. 

    “This is such an important grant because it supports the first steps toward translating this novel discovery into a new treatment that could give hope to so many people with pancreatic cancer,” says Heynen-Genel. “This grant helps us lay the groundwork to figure out how this research could be applied in the clinic.”

    The researchers will screen hundreds of thousands of molecules and identify a select few “hits” that have desirable biological effects and chemical properties. Then they will conduct other studies on these hits to see which have the most potential to fight pancreatic cancer with minimal side effects. By the end of the grant, the team will have several drug candidates that can be developed further toward anticancer therapies. 

    “We could find the next major breakthrough in pancreatic cancer treatment, but we have to put in the legwork now to find out,” says Heynen-Genel. “That’s what’s exciting about drug discovery. It feels like it has infinite potential.”

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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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  • Scientists Map Genetic Evolution of Chronic Lymphocytic Leukemia to Richter’s Syndrome

    Scientists Map Genetic Evolution of Chronic Lymphocytic Leukemia to Richter’s Syndrome

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    Newswise — Every year, up to 1% of patients with chronic lymphocytic leukemia (CLL), a slow-growing blood cancer, have their disease transform into a far more aggressive cancer, a form of lymphoma known as Richter’s Syndrome. For the most part, the genomic changes that underlie this metamorphosis and push it forward have been obscure, hindering advances in treatment. 

    In a new study, scientists at Dana-Farber and the Broad Institute of MIT and Harvard trace these changes in unprecedented detail, revealing for the first time the genomic differences between CLL and Richter’s, the molecular pathways by which Richter’s emerges, and the existence of multiple subtypes of the disease.

    The findings, presented today at the annual meeting of the American Society of Hematology (ASH) and published online in the journal Nature Medicine, not only break open what was once a “black box” of molecular change but point the way to an earlier diagnosis of the disease, when treatments may be more effective.

    “The treatments for CLL and Richter’s Syndrome are very different, so it’s critical that doctors be able to determine, as early as possible, when CLL has ‘crossed over’ to become Richter’s,” says study co-senior author Catherine Wu, MD, of Dana-Farber, the Broad Institute, and Brigham and Women’s Hospital. “The traditional method of diagnosing Richter’s has a number of shortcomings, which can lead to delays in patients’ receiving the appropriate treatment. Our findings in this study hold the promise of an earlier, more definitive diagnosis based on the molecular makeup of the tumor cells.”

    One of the biggest obstacles to diagnosing Richter’s Syndrome is that patients don’t have either CLL or Richter’s cells, but a mixture of both. And unlike CLL, which is diagnosed from a blood sample, a formal diagnosis of Richter’s requires a biopsy, in which a small piece of tissue is removed and examined under a microscope for telltale changes in the structure and markings of the cells. But because a biopsy collects tissue from just one area, it may find CLL cells but miss Richter’s cells lurking right nearby. As a result, a patient may have classic symptoms of Richter’s such as swollen lymph nodes, fever, night sweats, but the biopsy – which ultimately determines the diagnosis – indicates CLL.

    To understand Richter’s at the molecular level and track how it evolves from CLL, researchers began with tissue samples gathered from 52 patients over a period of years. Samples collected when the patients had CLL were paired with samples taken when they were diagnosed with Richter’s. The researchers then performed whole exome sequencing, reading the protein-coding sections of DNA in the samples.  Because the samples likely had a mix of cells, they used computational methods on these sequencing data to estimate the proportion of CLL and Richter’s cells in each one. Knowing the relative levels of different cell types within the samples, they were able to identify the genetic changes that drive the evolution from CLL to Richter’s.

    The researchers discovered a motley assortment of such changes, including mutations in multiple genes, missing or added copies of other genes, duplication of cell genomes, and ‘chromothripsis’, a splintering and haphazard reassembly of entire chromosomes.

    “We see myriad differences between CLL and Richter’s at the molecular level, with a much more complex genome in Richter’s, as well as additional driver events,” remarks study co-senior author, Dr. Gad Getz of the Broad Institute and Massachusetts General Hospital. “In addition, we’ve found that Richter’s exists in a number of different subtypes.”

    The subtypes are distinguished by their molecular signatures, the specific pattern of genomic anomalies within their cells. These DNA-level differences suggest that the subtypes arrived by taking different routes in evolving from CLL. “The formation of multiple subtypes can give us insights into the ‘archaeology’ of the disease: what was the molecular make-up of CLL before it transformed into one subtype or another?” Wu explains.

    Being able to identify different subtypes of Richter’s can be helpful in the clinic: patients with certain subtypes generally fare better than those with others, although the outlook at the present time is poor for all patients with Richter’s. Scientists hope that advances can improve those prospects.

    Plasma diagnosis

    Once researchers knew the genomic features of Richter’s, they explored whether the disease could be detected by analyzing DNA in patients’ plasma, the liquid portion of blood. They sequenced the DNA in 46 plasma samples from 24 patients with Richter’s. The samples had been collected over a period of years, beginning within three years of a diagnosis of Richter’s and extending through treatment and relapse of the disease. The researchers then sequenced the DNA floating freely within the samples. “We found that genomic features of Richter’s were indeed detectable in the plasma,” Wu relates.

    “We then asked whether such changes could be detected before patients had been diagnosed with Richter’s based on a biopsy,” she continues. “For some patients, we clearly detected Richter’s-related DNA alterations in plasma that had been collected one to ten months prior to their Richter’s diagnosis – a time at which they had been undergoing treatment for what was presumed to be aggressive CLL.” The upshot is that it may become possible to diagnose Richter’s through a simple blood test, potentially earlier than it would show up on a biopsy and at a stage where it may be more treatable.

    “The current therapies for Richter’s are of very limited effectiveness, yet there is hope that patients may benefit from novel, more effective agents. Clinical trials of these agents and of stem cell transplant can explore that promise,” Wu notes. “By the time Richter’s is diagnosed, however, patients may be very sick, at which point transplant or other new therapies may not be an option. So detecting it early may make a critical difference.”

    Learning the molecular hallmarks of Richter’s led researchers to one further discovery. In a substantial portion of patients, their Richter’s cells didn’t share a genetic history with their CLL cells, meaning Richter’s arose independently, with no connection to the earlier disease.

    “Looking ahead to future work, we would like to analyze even larger cohorts of RS patients to obtain a comprehensive characterization of the genomic and microenvironmental landscape of RS; from this, we can discover new and robust therapeutic targets as well as refined molecular subtypes, getting us closer to applying precision medicine to this disease,” adds Dr. Getz

    “Our findings suggest that in many patients, the genomic changes in CLL that lead to Richter’s occur before patients develop symptoms of lymphoma,” Wu says. “Being able to trace the transition from CLL to Richter’s at a molecular level impacts not only our understanding of the disease but, potentially, our ability to treat it and improve outcomes for patients.”

    The co-senior authors of the study are Gad Getz, PhD, of Massachusetts General Hospital and the Broad Institute, and Stephan Stilgenbauer, MD, of Ulm University, Ulm, Germany. The lead authors are Erin Parry, MD, PhD, of Dana-Farber and the Broad Institute; Ignaty Leshchiner, PhD, of the Broad Institute and Boston University School of Medicine; and Romain Guieze, MD, PhD, of Dana-Farber, the Broad Institute, CHU de Clermont-Ferrand and Université Clermont Auvergne, both in France. The co-authors are: Camilla Lemvigh, Shanye Yin, PhD, Teddy Huang, Shuqiang Li, PhD, Geoff Fell, Robert Redd, Neil Ruthen, Stacey Fernandes, Annabelle J Anandappa, MD, Kenneth J. Livak, PhD, Donna Neuberg, ScD, Matthew S. Davids, MD, and Jennifer R. Brown, MD, PhD, of Dana-Farber; Noelia Purroy-Zuriguel, MD, PhD, of Dana-Farber and the Broad Institute; Connor Johnson, Conor Messer, Liang Li, Daniel Rosebrock, Kara Slowik, Raquel Jacobs, Ziao Lin, Binyamin A. Knisbacher, PhD, Dimitri Livitz, Liudmilla Elagina, Amaro Taylor-Weiner, PhD, Bria Persaud, Aina Martinez, Jialin Ma, Julian Hess, Brian P. Danysh, PhD, and Chip Stewart, PhD, of the Broad Institute; Eugen Tausch, MD, and Christof Schneider of Ulm University; Sameer A. Parikh, MD, and Neil E. Kay, MD, of the Mayo Clinic; Julien Broséus, MD, PhD, Sébastien Hergelant, and Pierre Feugier of Université de Lorraine, Nancy, France; Filippo Utro, PhD, Chaya Levovitz, MD, PhD, Kahn Rhrissorrakrai, PhD, and Laxmi Parida, PhD, of IBM Research, Yorktown Heights, N.Y.; Laura Z Rassenti,, PhD, and Thomas J Kipps MD, PhD, of Moores Cancer Center, Medicine, University of California, San Diego; Nitin Jain, MD, and William Wierda, MD, PhD, of the University of Texas MD Anderson Cancer Center; and Florence Cymbalista, MD, PhD, of Université Sorbonne Paris Nord, Bobigny, France.

    The study was supported by the National Institutes of Health/National Cancer Institute (grants # P01 CA206978, 1U10CA180861-01, R01 CA 213442, and P01 CA 206978); a DDCF Physician-Scientist Fellowship; Dana-Farber Flames FLAIR fellowship; ASCO Conquer Cancer Young Investigator Award; the Broad/IBM Cancer Resistance Research Project; the Fishman Family Fund; Force Hemato; a long-term EMBO fellowship (ALTF 14-2018); Deutsche Forschungsgemeinschaft; an NCI Research Specialist Award; and the Melton Family Foundation.

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    Dana-Farber Cancer Institute

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  • Understanding How the Perception of Risks and Benefits Influence Cancer Clinical Trial Withdrawal Outcomes

    Understanding How the Perception of Risks and Benefits Influence Cancer Clinical Trial Withdrawal Outcomes

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    Newswise — PHILADELPHIA (December 7, 2022) – While people with cancer have options to participate in cancer clinical trials (CCTs), it can be challenging when they encounter difficulties enrolling and remaining in the trial. Trial withdrawal, although every participant’s right, can thwart study goals and hamper advancing novel treatments.

    Until now, little attention has focused on what influences retention after participants are enrolled in the trial, especially the role of perceived benefits and burdens. A new investigation from the University of Pennsylvania School of Nursing (Penn Nursing) has examined the association between patients’ perceived benefits and burdens of research participation and CCT retention. It found that patients perceived important benefits from CCT participation, which was associated with trial retention, even among those who also perceived substantial burdens. 

    “The findings of how perceptions of benefits and burdens were associated with CCT withdrawal outcomes provide novel and foundational evidence of the importance of understanding these perceptions for trial retention,” explains Connie M. Ulrich, PhD, RN, FAAN, Lillian S. Brunner Chair in Medical and Surgical Nursing, Professor of Nursing and Professor of Medical Ethics and Health Policy at Penn Nursing. Ulrich is the lead investigator of the study.

    The study found that when perceived benefits were equal to or greater than perceived burdens, participants were less likely to withdraw than those who perceived the burdens to be greater than the benefits. How participants think about benefits and burdens in a research trial may differ from how researchers and IRBs discern the trial’s acceptability.

    “Protection of human participants is critical, but more research is needed on how participants perceive benefits, the different types and categories of benefits, and implications of perceived benefits for retention to elucidate the role of benefits compared with the risks and burdens that participants are asked to bear,” says Ulrich.

    The results of the study have been published in the article “Association of Perceived Benefit or Burden of Research Participation With Participants’ Withdrawal From Cancer Clinical Trials,” available online on JAMA Network. Coauthors of the article include: Mary D. Naylor, PhD, RN, FAAN, Marian S. Ware Professor in Gerontology Director of the NewCourtland Center for Transitions and Health, Therese S. Richmond, PhD, RN, FAAN, Andrea B. Laporte Professor of Nursing and Associate Dean for Research & Innovation, and Liming Huang, all of Penn Nursing;  Sarah J. Ratcliffe of the University of Virginia; Qiuping Zhou of the George Washington University; Camille Hochheimer of the Colorado School of Public Health; Thomas Gordon of the University of Massachusetts; Kathleen Knafl of the University of North Carolina at Chapel Hill; Marilyn M. Schapira of the Perelman School of Medicine at the University of Pennsylvania and the Veterans Affairs Medical Center; Christine Grady of the National Institutes of Health; and Jun J. Mao of Memorial Sloan Kettering.  

    Ulrich was supported in part by grant R01CA196131 from the National Cancer Institute of the NIH (NCI/NIH). Ratcliffe was supported in part by grant R01-NR014865 from the NCI/NIH. Richmond was supported in part by grant R01CA196131 from the NCI/NIH. Mao was supported in part by grants P30CA008748 and R01CA240417 from the NCI/NIH. 

    # # #

    About the University of Pennsylvania School of Nursing

    The University of Pennsylvania School of Nursing is one of the world’s leading schools of nursing. For the seventh year in a row, it is ranked the #1 nursing school in the world by QS University. In a first for any undergraduate Bachelor of Science in Nursing (BSN) program in the country, our BSN program is ranked # 1 in the 2022 U.S. News & World Report’s Best Colleges rankings. Penn Nursing is also consistently ranked highly in the U.S. News & World Report annual list of best graduate schools and is ranked as one of the top schools of nursing in funding from the National Institutes of Health. Penn Nursing prepares nurse scientists and nurse leaders to meet the health needs of a global society through innovation in research, education, and practice. Follow Penn Nursing on: Facebook, Twitter, LinkedIn, & Instagram.  

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    University of Pennsylvania School of Nursing

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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.

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    University of Texas M. D. Anderson Cancer Center

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