• IU School of Medicine findings set new standard for use of blood-based biomarkers in clinical trials for prediction of cancer recurrence

    IU School of Medicine findings set new standard for use of blood-based biomarkers in clinical trials for prediction of cancer recurrence

    INDIANAPOLIS– Indiana University School of Medicine researchers Milan Radovich, PhD, and Bryan Schneider, MD, have discovered that the presence of circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs) in the plasma of women’s blood who have undergone chemotherapy prior to surgery for the treatment of stage 1, 2 or 3 triple negative breast cancer are critical indicators for the prediction of disease recurrence and disease-free survival. Their findings, published today in the prestigious international peer-reviewed journal, JAMA Oncology allow for a stratification of patients in clinical trials around the world, that didn’t exist prior to their discovery.  The pair also spoke about their findings as part of a JAMA Oncology podcast

    “These findings from the Vera Bradley Foundation Center for Breast Cancer Research, located at IU School of Medicine, enable a scientific basis for predicting relapse and disease-free survival, which are both important questions for women who live in constant fear of their disease returning,” said Jay L. Hess, MD, PhD, MHSA and dean of IU School of Medicine. “The discoveries reflect our long history as  leaders in genomics, bioinformatics and medical innovation.”

    Specifically, Radovich and Schneider, who are also researchers at the IU Melvin and Bren Simon Comprehensive Cancer Center, along with colleagues from the Hoosier Cancer Research Network, analyzed plasma samples taken from the blood of 196 women, as part of a preplanned secondary analysis of women who were participants in clinical study BRE12-158. This is the largest known data set of patients to date. 

    They discovered that the detection of ctDNA was significantly associated with poorer outcomes on three important measures for patients: distant disease-free survival, disease-free survival and overall survival. When the presence of ctDNA was combined with the presence of CTCs, the outcomes were even worse.

    • At two years post-surgery and chemotherapy, distant disease-free survival for women with the presence of ctDNA in their blood was 56 percent, when compared with 81 percent for women without ctDNA
    • Patients with the presence of both ctDNA and CTCs at two years had a 52 percent likelihood of distant disease-free survival versus 89 percent who were negative for both markers.

    Approximately one-third of patients will achieve remission from their triple negative breast cancer, following surgery and chemotherapy. However, two-thirds will have residual disease, putting them at high risk of relapse. These findings will be the focus of the PERSEVERE study, which will stratify women with triple negative breast cancer based on being ctDNA positive and assign them a targeted therapy matched to the patient’s genomic sequencing. The study is powered to help discover a personalized therapy for patients at high risk for relapse and for whom no treatments currently exist. More information about the PERSEVERE study will be provided in the coming months.

    “A diagnosis of triple negative breast cancer is very scary to the patient. The discovery and utilization of circulating tumor DNA and circulating tumor cells to better predict recurrence, by Drs. Schneider and Radovich, has provided a huge step forward toward more certainty for treatment decision making,” said Mary Lou Smith, co-founder of the Research Advocacy Network. “This significant scientific advancement will help personalize treatments for those still battling residual disease.”

    “Since uncovering these findings in women diagnosed with triple negative breast cancer, we have learned that others are applying this stratification of patients based on ctDNA and CTCs to other cancers, including breast and colon,” said Radovich.

    “This is an important step forward in the treatment of women with triple negative breast cancer, who have not had much scientific evidence to point to—until now—for treatment of their disease,” said Schneider. “We are going to use these findings and continue on until we find a treatment that works for each individual woman. This effort not only involves finding the best way to kill cancer, but to minimize side effects.”

    As a further testament to the significance of these findings, Radovich presented the initial findings as part of an oral, plenary session on December 13, 2019, at the San Antonio Breast Cancer Symposium, the most influential gathering of breast cancer researchers and physicians in the world.

    Access the full media kit.

    Study BRE12-158 was funded by the Vera Bradley Foundation for Breast Cancer and the Walther Cancer Foundation. It is part of the Indiana University Precision Health Initiative Grand Challenge. The study was managed by the Hoosier Cancer Research Network and enrolled at 22 clinical sites across the United States.

    Media contact: Christine Drury, cldrury@iu.edu, 317-385-9227

    # # #

    IU School of Medicine is the largest medical school in the U.S. and is annually ranked among the top medical schools in the nation by U.S. News & World Report. The school offers high-quality medical education, access to leading medical research and rich campus life in nine Indiana cities, including rural and urban locations consistently recognized for livability.

  • IU cancer researcher earns $1.6 million NCI grant for multiple myeloma bone disease therapies

    IU cancer researcher earns $1.6 million NCI grant for multiple myeloma bone disease therapies

    INDIANAPOLIS – An Indiana University Melvin and Bren Simon Comprehensive Cancer Center researcher has been awarded a five-year, $1.6 million grant from the National Cancer Institute to study ways to build bone and decrease tumor growth in multiple myeloma bone disease.

    Multiple myeloma is a blood cancer that begins in plasma cells within the bone marrow. As the multiple myeloma cells build up, they form tumors and can damage and weaken bones.

    G. David Roodman, MD, PhD, distinguished professor at IU School of Medicine, is leading the research to investigate a molecule developed with collaborators at the University of Pittsburgh that could repair bone, decrease tumors and improve outcomes for multiple myeloma patients on specific targeted therapies.

    “We've been very interested in understanding the mechanisms underlying the horrific bone disease associated with multiple myeloma, which occurs in up to about 85 percent of patients and causes devastating pathologic fractures, bone pain and impacts survival,” Roodman said.

    Previously, Roodman and colleagues had shown the importance of the marrow microenvironment on the growth of the tumor cells in the bone destructive process. They, with collaborators at the University of Pittsburgh, developed a small molecule called XRK3F2 to target that bone disease. Animal models and preclinical tissue models have shown that the molecule could have an important role also in stopping drug resistance in myeloma cells.

    “This grant allows us to look at using a small molecule to show how we can overcome resistance to some of the most potent drugs that are in use for myeloma,” Roodman said. “Many patients develop drug resistance over time, and it becomes very difficult to treat them.”

    Among newer treatments developed for multiple myeloma are targeted therapies called proteasome inhibitors, including the drugs Bortezomib and Carfilzomib. In models developed by Roodman’s research team, the XRK3F2 molecule enhanced the effects of these drugs in preclinical models of multiple myeloma.

    The molecule also caused new bone formation in animal models, which could lead to treatments for healing bone lesions. Currently, there are no safe therapies to build bone mass that are approved for multiple myeloma bone disease.

    Roodman and his team will further explore the XRK3F2 molecule to understand the mechanism responsible for its effects on multiple myeloma cells and its potential for new therapies for the disease.


    IU School of Medicine is the largest medical school in the U.S. and is annually ranked among the top medical schools in the nation by U.S. News & World Report. The school offers high-quality medical education, access to leading medical research and rich campus life in nine Indiana cities, including rural and urban locations consistently recognized for livability.

  • Cancer center researchers identify checkpoint target for colorectal cancer immunotherapy

    Cancer center researchers identify checkpoint target for colorectal cancer immunotherapy

    Researchers at the Indiana University Melvin and Bren Simon Comprehensive Cancer Center have identified a target for colorectal cancer immunotherapy.

    Immunotherapy uses the body’s immune system to target and destroy cancer cells. Considered the future of cancer treatment, immunotherapy is less toxic than chemotherapy. Colorectal cancer is the third most common cancer among men and women, yet chemotherapy remains the standard of care as limited numbers of patients respond to current immunotherapy treatment options.

    The findings published May 7 in JCI Insight could provide additional treatments for a larger number of colorectal cancer patients via a new immunotherapy pathway. Researchers identified ST2 as a novel checkpoint molecule that could help T cells become more effective.

    The research is a collaboration between IU School of Medicine cancer researchers Xiongbin Lu, PhD, Vera Bradley Foundation Professor of Breast Cancer Innovation and of Medical and Molecular Genetics, and Sophie Paczesny, MD, PhD, Nora Letzter Professor of Pediatrics and of Microbiology and Immunology.

    Immune checkpoints are an essential part of the immune system with the role of preventing immune cells from destroying healthy cells. T cells are immune system cells that attack foreign invaders such as infections and can help fight cancer. But cancer is tricky, and often the tumor microenvironment creates ways to prevent T cells from attacking cancer cells by misusing several factors including the activation of checkpoint molecules.

    Within the tumor microenvironment, the body’s immune system knows something is wrong and sends a stress signal such as the alarmin IL-33, which brings in immune cells called macrophages that express ST2 (the receptor for IL-33) to help. What is at first a “good” response is quickly overwhelmed and the macrophages become the enemy in fighting colon cancer.

    The authors investigated using patient tumor genetic data and found that T-cell functionality, one of the key factors in fighting the cancer using the adaptive immune responses, is reduced in patients displaying high ST2 levels. Using tumor tissue samples from IU Simon Comprehensive Cancer Center tissue bank, researchers found abundant expression of ST2 in macrophages in tumor tissue samples from early to late-stage colorectal cancer.

    “In all of the patient samples, we were able to identify ST2 expressing macrophages, which would potentially mean that targeting these ST2 macrophages would be relevant to the patients,” Kevin Van der Jeught, PhD, said. Van der Jeught is a post-doctoral researcher in Lu’s lab and first author of this study.

    In preclinical mouse models, researchers found that by targeting the ST2-expressing macrophages, they were able to slow tumor growth. By depleting these inhibitory cells, the T cells became more active in fighting cancer.


    Collaboration connects cancer research interests

    Research collaborator and scientist at the Herman B Wells Center for Pediatric Research, Paczesny’s previous research led to the discovery of ST2 and is the subject of her National Cancer Institute “Cancer Moonshot” grant focusing on immunotherapy for pediatric acute myeloid leukemia (AML). While leukemia and colorectal cancer are very different diseases, researchers have found commonality and collaboration in the ST2 protein.

    “This research is bringing together the pathway in two different diseases,” Paczesny said.

    Lu’s research focuses on cancer cell biology in diseases such as triple negative breast cancer and colorectal cancer.

    “We have to develop new tools and new approaches for solid tumors, and this is the kind of collaboration we need for advancing future treatments,” Lu said. Researchers from two other institutions, the University of Maryland’s Marlene and Stewart Greenebaum Comprehensive Cancer Center and the VIB-UGent Center for Inflammation Research in Belgium, have contributed to this publication.

    Researchers also are exploring combination therapy with existing immunotherapy, such as PD-1 checkpoint inhibitors, which work to boost T cells directly, while attacking ST2 on macrophage cells increased T cells by stopping the inhibitors.

    “Potentially through a combination of two checkpoints at work on different immune cells, we could enhance the current response rates,” Van der Jeught said.

    The researchers plan to explore these findings further and pursue the development of ST2 for cancer immunotherapy.

    Additional authors with Van der Jeught, Paczesny and Lu are IU School of Medicine researchers Yifan Sun; Yuanzhang Fang, PhD; Zhuolong Zhou, PhD; Hua Jiang, PhD; Tao Yu, PhD; Jinfeng Yang, PhD; Malgorzata M Kamocka, PhD; Ka Man So; Yujing Li, PhD; Haniyeh Eyvani; George E Sandusky, DVM, PhD; and Michael Frieden; Xinna Zhang, PhD, and Chi Zhang, PhD, IU Simon Comprehensive Cancer Center; Harald Braun, PhD, and Rudi Beyaert, PhD, Ghent University, Ghent, Belgium; and Xiaoming He, PhD, Greenebaum Comprehensive Cancer Center, University of Maryland.

    This research was supported by IU School of Medicine Strategic Research Initiative fund; NIH R01CA203737 (Lu); and NIH U01CA232491 (Paczesny). A supplemental grant application has been submitted to NCI for funding further studies in hereditary non-polyposis colorectal cancer also called Lynch syndrome.

  • Researchers develop publication with collaborator quarantined in China during COVID-19 outbreak

    Researchers develop publication with collaborator quarantined in China during COVID-19 outbreak

    Putting together research for publication can be a challenging and time-consuming process, heightened even further because of the current COVID-19 situation, during which non-essential labs at Indiana University School of Medicine have been hibernated and many researchers are now working separately and remotely, instead of collaborating within the same space. Despite those obstacles, Jie Zhang, PhD, Jun Cheng PhD, and Kun Huang, PhD, had their research published in Nature Communications on April 14, which is an even more significant feat considering one of their leading authors has been quarantined in Wuhan, China for the last two months of their work.

    The study that brought about this opportunity for publication was led by Zhang, who is an assistant professor of medical and molecular genetics. It focuses on the application of machine learning and image analysis to help researchers distinguish a rare subtype of kidney cancer (translocational renal cell carcinoma, or tRCC) from other subtypes by examining the features of cells and tissues on a microscopic level. Zhang said the structural similarities have caused a high rate of misdiagnosis. Within this publication, the researchers studied 74 tRCC samples, which constitutes the largest tRCC collection in the world.

    “The phenotype of this tRCC looks very much like clear cell renal cell carcinoma, or ccRCC, the most common type of renal cell carcinoma, so it’s kind of difficult for pathologists to distinguish between the two,” said Zhang. “To improve that, we tried to use the machine-learning technique, feeding in the digitized pathological image data to the analysis pipeline to train the computer to extract the features related to tRCC. This will help pathologists confirm the case, instead of just relying on their eyes.”

    Jun Cheng, PhDThe first author of this paper, Jun Cheng, PhD, started working with Zhang and Huang back in 2016, while he was a visiting PhD student from China. Cheng visited for the first time when Zhang and Huang were researchers at Ohio State University, before they joined IU School of Medicine, and has also visited them since they transitioned to their current roles. Cheng is currently an assistant professor at Shenzhen University and had traveled to his hometown of Wuhan for winter vacation.

    “I was planning to stay at home for 10 days,” said Cheng. “Three days later, the whole city of Wuhan was in lockdown (due to concerns of COVID-19) and the lockdown lasted for over two months.”

    The city of Wuhan became the epicenter of the pandemic, with more than 50,000 confirmed cases of COVID-19 among the population of 11 million people. As he was working to revise their publication, Cheng could not return to his lab at Shenzhen University, since teachers and students who left for vacation weren’t allowed to go back due to the pandemic. He only had a laptop at his home, but needed a high-performance computer to conduct data analyses.

    “Fortunately, one student in my lab didn't go home and stayed in school during winter vacation,” said Cheng. “She helped boot the computer in my lab and then I did all the experiments on it remotely.”

    Cheng also needed to repeat some of the analysis for the revision, which required a transfer of previously downloaded public data to China from Huang’s lab in Indiana, and it took a week to complete the data transfer.

    “It was quite stressful to revise the publication during the quarantine, but finally we made it,” said Cheng.

    Huang described this publication as a true team science effort, involving both internal and international collaborations, both of which he said are essential. Liang Cheng, MD, Virgil Moon Professor of Pathology from IU School of Medicine and one of the corresponding authors in this paper, was able to collect additional tRCC and ccRCC samples within two weeks from a collaborator in Michigan for the additional analysis, which itself was an amazing accomplishment.

    “In many cases, we collaborate internationally because there is a huge innovation base that can help with our research,” said Huang, who is also the Director of Data Sciences and Informatics for the IU Precision Health Initiative. “Even in difficult times, as long as we have enough resources and means of communication, we can still carry out collaborative research.”

    While cancer has traditionally been characterized by the location of the disease, this research focuses on renal cancer based on the genetic markers instead. This study was supported in part by the IU Precision Health Initiative.

    The city of Wuhan was reopened last week.

  • IU cancer researcher identifies new areas in human genomes linked to skin cancer risk

    IU cancer researcher identifies new areas in human genomes linked to skin cancer risk

    INDIANAPOLIS — An Indiana University cancer researcher has identified eight new genomic regions that increase a person’s risk for skin cancer.

    Jiali Han, Ph.D., and colleagues discovered eight new loci—locations on a person’s genome—that are susceptible to the development of squamous cell skin cancer. Han is the Rachel Cecile Efroymson Professor in Cancer Research at IU School of Medicine, professor and chair of the Department of Epidemiology at the IU Richard M. Fairbanks School of Public Health at IUPUI, and a researcher at the Indiana University Melvin and Bren Simon Cancer Center.

    Researchers previously identified 14 loci with increased risk for squamous cell skin cancer. This study confirmed those findings while adding eight new genomic locations, bringing the total identified risk loci to 22. Their research is published this month online in Nature Communications.

    “This is the largest genetic-associated study for squamous cell carcinoma of the skin,” Han, an epidemiologist, said. “Our multidisciplinary research sheds light on new biology and the etiology of squamous cell carcinoma, confirming some important genes and also identifying genes involved in this particular cancer development.”

    Han and colleagues analyzed six international cohorts totaling approximately 20,000 squamous cell skin cancer cases and 680,000 controls, or people who haven’t had squamous cell skin cancer. More than one-third of the genomic data came from genetic testing company 23andMe research participants. Additional datasets came from the Nurse’s Health Study, Health Professionals Follow-up Study, the Icelandic Cancer Registry and the Ohio State University Division of Human Genetics sample bank.

    Research findings confirmed that pigmentation genes can also be a person’s skin cancer susceptibility gene, but they also identified additional molecular pathways.

    “We can certainly say there is some genetic overlap between squamous cell carcinoma, basal cell carcinoma and melanoma—the three major types of skin cancer—but we also found some genes are specific for squamous cell carcinoma,” Han said.

    Squamous cell and basal cell are also known as non-melanoma skin cancers. Both usually respond to treatment and rarely spread to other parts of the body, according to the National Cancer Institute. Melanoma is more aggressive, however, and can spread to other parts of the body if it’s not diagnosed early.

    Physical genomic traits such as fair skin, freckles, blue eyes and brown hair were associated with the risk loci. Researchers have long known that fair skin and sun exposure are risk factors for squamous cell skin cancer.

    “Avoiding sun exposure is always the primary prevention strategy, regardless of your skin pigmentation,” Han said.

    Han and collaborators are continuing to build the population sample to identify more risk loci. Even with the 22 genomic regions identified, the study found those explain only 8.5 percent of the heritable risk for squamous cell skin cancer.

    Kativa Sarin, M.D., Stanford University School of Medicine, is the co-lead author. Additional authors of the study are Yuan Lin and Wenting Wu, Fairbanks School of Public Health; Roxana Daneshjou, Adam Rubin, Paul Khavari and Alice Whitemore, Stanford University; Andrey Ziyatdinov and Peter Kraft, Harvard T.H. Chan School of Public Health; Gudmar Thorleifsson and Simon N. Stacey, deCODE genetics/Amgen Inc., Reykjavik, Iceland; Luba M. Pardo, Tamar Nijsten, Andre Uitterlinden, Erasmus University Medical Center, Rotterdam, The Netherlands; Amanda E. Toland, Ohio State University Comprehensive Cancer Center; Jon H. Olafsson, Bardur Sigurgeirsson and Kristin Thorisdottir, Landspitali-University Hospital and University of Iceland, Reykjavik, Iceland; Eric Jorgensen, Kaiser Permanente Northern California; Kari Stefansson, University of Iceland; and Maryam M. Asgari, Massachusetts General Hospital.

    The study was supported in part by grants from the National Human Genome Research Institute of the National Institutes of Health (grant number R44HG006981), the National Cancer Institute (R01 CA49449, P01 CA87969, UM1 CA186107, UM1 CA167552, R03 CA219779, K23 CA211793) and Indianapolis-based Walther Cancer Foundation.

  • IU Simon Cancer Center researchers receive $3 million in NIH grants to investigate cell functions within bone marrow

    IU Simon Cancer Center researchers receive $3 million in NIH grants to investigate cell functions within bone marrow

    INDIANAPOLIS — More than $3 million from the National Institutes of Health will allow Indiana University Melvin and Bren Simon Cancer Center researchers to improve understanding of the complex system of how hematopoietic stem cells (HSC) survive and sustain their function in the bone marrow.

    Edward F. Srour, Ph.D., the Robert J. and Annie S. Rohn Professor of Leukemia Research, and Melissa A. Kacena, Ph.D., professor of orthopaedic surgery, are building on a decade of research collaboration on how bone cells help HSC function. Both Srour and Kacena are Indiana University School of Medicine faculty.

    HSC, which produce red and white blood cells, reside in the bone marrow in the core of bones. The complex system of multiple cell types that are responsible for maintaining those stem cells is called the hematopoietic niche.

    “Years ago, we discovered that a molecule named CD166 is important for the maintenance of stem cells because it is also expressed on immature osteoblasts, the bone-forming cells that are an important component of the hematopoietic niche,” Srour said. Both young osteoblasts and stem cells interact together through CD166 to maintain stem cell function.

    Researchers know that the CD166 molecule is critical because stem cells lose activity without it, but for which cells is it most important and which don’t need it?

    Video extra: Why a single molecule called CD166 could unlock new cancer therapies

    With a $1.7 million grant from the National Institutes of Health, Srour and colleagues will delete CD166 from different cell types found in the hematopoietic niche to figure out where the molecule is essential and where it is not.

    “Molecules and their receptors are basically like a key and a lock; you have a key on one cell and a lock on another cell,” Srour said. “With CD166, it is both the key and the lock—it binds to itself. We have to find who carries the most important lock and what does the turning of the key in that lock do to activate the cell.”

    Separating look-alike cells

    IU Simon Cancer Center researchers are also investigating another cell type formed in the hematopoietic niche called osteomacs, which are a specialized bone-resident macrophage. Macrophages are vital to the immune system with the job of engulfing and destroying foreign pathogens and sometimes cancer cells.

    While macrophages reside in every tissue in the body, their jobs differ a little depending on location. Working inside the bones are specialized macrophages called osteomacs.

    “We found that osteomacs play an important role in sustaining the stem cell function within the niche of the bone marrow,” Srour said. “The major struggle we have with these cells is they look like and function like bone marrow macrophages, so there is no easy way for us to separate one from the other.”

    With a five-year, $1.5 million grant, Srour and colleagues aim to identify a molecule that allows them to separate osteomacs from macrophages.

    In the search to find a distinguishing marker, researchers found that osteomacs—unlike other macrophages—express CD166. The molecule is vital to osteomacs, too; osteomacs that don’t have it lose their function. Now Srour wants to know why and form a better understanding of osteomacs’ role within the complex bone marrow environment.

    Srour and IU researchers also have found that CD166 also is expressed on a rare population of myeloma cells that can initiate and make myeloma more aggressive. Multiple myeloma is a blood cancer of plasma cells within the bone marrow. Understanding the role of different cells in sustaining myeloma and identifying how to block CD166 in important cells of the cancer may provide pathways to stopping or slowing some cancers.

    “We believe these are the cancer-initiating or so-called cancer stem cells,” Srour said.

    Beyond myeloma, CD166 is present in many metastatic cancers, including breast cancer and pancreatic cancer. “The overexpression of that molecule is associated with the ability of cancer cells to metastasize (to spread),” Srour said.


  • IU School of Medicine hosting “Us vs. HPV” webinars for HPV Prevention Week

    IU School of Medicine hosting “Us vs. HPV” webinars for HPV Prevention Week

    The Indiana University School of Medicine National Center of Excellence in Women’s Health is getting ready for a week of raising awareness about human papilloma virus (HPV).

    “We have to protect our community,” said Theresa Rohr-Kirchgraber, MD, FACP, FAMWA, executive director of the National Center of Excellence. “We have to protect our children, and we need to make our Hoosiers healthier, happier and lead productive lives.”

    Each year, more than 12,000 women are diagnosed with cervical cancer, which is caused by HPV. About 90 percent of those cases could be prevented with the Gardasil HPV vaccine, which was partially developed by IU School of Medicine researchers in the 1990s. HPV can also lead to some head and neck cancers, anal cancer and anal warts in both men and women.

    HPV Prevention Week is a global initiative against HPV and the cancers HPV causes. A week of webinars, called “Us vs. HPV,” are scheduled every day from January 27-31. The webinars are hosted by the American Medical Women’s Association (AMWA), Global Initiative Against HPV and Cervical Cancer (GIAHC) and IU School of Medicine National Center of Excellence. Topics include community initiatives and challenges, medical societies’ efforts against HPV, gathering momentum for the global elimination of cervical cancer, HPV-associated head and neck cancers and how HPV affects us all.

    Rohr-Kirchgraber is one of the moderators for this year’s event, which is free and open to anyone to watch and listen online.

    “We want you all to listen and learn, and we invite you to send in questions and share your thoughts and ideas,” Rohr-Kirchgraber said. “We will also have testimony from patients who have been through some of these cancers so that they can share with you directly the impact of having to deal with these types of cancers and diseases.”

    Other speakers include international physicians and scientists actively researching ways to prevent and treat HPV and HPV-related cancers. To learn more about the agenda and to register for the webinars, visit the event registration webpage.

  • Indiana University School of Medicine researchers discover emerging combination therapy that halts tumor growth based on Tyler Trent’s cell lines

    Indiana University School of Medicine researchers discover emerging combination therapy that halts tumor growth based on Tyler Trent’s cell lines

    INDIANAPOLIS – Researchers at Indiana University School of Medicine have found a combination therapy that significantly slows tumor growth in models, built from cells taken from Tyler Trent’s tumors. Tyler was a Purdue University student and football superfan who died on January 1, 2019, after waging a long and valiant fight against an aggressive form of bone cancer.

    The researchers, led by Karen E. Pollok, PhD, found a variation in Tyler’s tumors (TT1 and TT2) called the MYC-RAD21 signature, which has been found in tumors that tend to recur. Pollok says there are two drugs that can block its effects, a Chk1 inhibitor (pronounced: “check-one” inhibitor) and a bromodomain inhibitor. Her team tested each of those drugs individually, as well as in combination.

    “What we found in Tyler’s model is we can take one of these drugs, the Chk1 inhibitor or the bromodomain inhibitor, and we can administer it in models with the TT2 tumor and we get the tumors to stop growing some, compared to a control,” said Pollok. “However, when we put the two drugs together, we block the growth of these tumors substantially.”

    Pollok and her team found that the combination therapy worked during a four-week treatment, but the tumor started growing again after stopping the therapy. They also determined that the treatment was well-tolerated. Pollok says they are very pleased with the results so far.

    “Tyler Trent has truly left us a legacy,” said Pollok. “While we still have much work to do, we are hopeful that new therapies for osteosarcoma will be possible in the near future.”

    Finding a cure for pediatric sarcomas, including osteosarcoma, is one of the focuses of the Indiana University Grand Challenges Precision Health Initiative. In addition, the number one fundraising priority of Riley Children’s Foundation, the fundraising arm for Riley Hospital for Children at IU Health, is pediatric research. The work is being done at the Herman B Wells Center for Pediatric Research at IU School of Medicine. During Thursday’s media availability at the Wells Center, Tyler’s parents, Kelly and Tony, will also share their hopes for a cure as they honor their son’s memory.

    The researchers’ next steps include better understanding how the tumors adapt to the treatments and optimizing the combination therapy.

    Tyler’s legacy as a research advocate started years ago while he was a patient at Riley Children’s Health. He donated several tumor samples to cancer researchers at IU School of Medicine and nationally advocated that others do the same.

    Tyler also encouraged people to donate money to support research. People have donated millions of dollars for cancer research in Tyler’s name, including approximately $180,000 for the Tyler Trent Cancer Research Endowment for Riley Hospital. The Trent family and Riley Children’s Foundation worked together to create the endowment fund, which supports pediatric research being conducted by IU School of Medicine researchers.

    Click here for media kit, including graphics to illustrate effects of combination therapy.

  • On ‘Sound Medicine’: Lyme disease, why we sleep, and tips for best care in the ER

    On ‘Sound Medicine’: Lyme disease, why we sleep, and tips for best care in the ER

    INDIANAPOLIS — The “Sound Medicine” program for April 27 includes segments about Lyme disease in both humans and dogs, how to ease the symptoms of breast cancer, and ways to get the best care in the emergency room.

    How can people avoid tick-borne illnesses? In 2013, the CDC reported that 300,000 people were diagnosed with Lyme disease, with only 30,000 cases being reported to the CDC. Paul Mead, M.D., the chief of epidemiology and surveillance for the CDC’s Lyme disease program, discusses the discrepancy in the number of cases and the number reported to the CDC, the lingering symptoms of Lyme disease, and the best ways to avoid tick-borne illnesses.

    Do you know dogs can get Lyme disease? As part of the healthy pets series, Liz Murphy, DVM, talks about Lyme disease in dogs. Lyme disease is spread to both humans and dogs by the black-legged tick, or deer tick. Dr. Murphy joins “Sound Medicine” to discuss how dogs contract Lyme disease, what symptoms pet owners should look for, and a vaccine that can prevent Lyme disease in dogs.

    Why do we need sleep? Researchers at the University of Wisconsin have developed a hypothesis that explains why humans need sleep. The synaptic homeostasis hypothesis, SHY, predicts that the brain needs time to rest in order to process information absorbed during the day. Chiara Cirelli, M.D., Ph.D., who helped develop the SHY hypothesis, joins “Sound Medicine” to discuss why we sleep, why the brain needs rest, and what the brain does while we’re sleeping .

    Can yoga ease the discomfort of breast cancer? A recent study published in the Journal of Clinical Oncology found that the focus on meditation and deep breathing in yoga could help reduce fatigue and inflammation for breast cancer patients. Kathy Miller, M.D., discusses when it’s safe for breast cancer patients to begin exercising and why yoga is the best choice for patients seeking relief. Dr.  Miller is the co-leader of the breast cancer program at the IU Simon Cancer Center and an associate professor at the IU School of Medicine.

    How can patients improve their visit to the emergency room? Leana Wen, M.D., M.Sc., recently published an article on Slate titled, “The 10 Types of ER Patients.” In the article, Dr. Wen describes the 10  patient behaviors she commonly sees in the emergency room. Dr. Wen joins “Sound Medicine” to explain how a trip to the emergency room can be improved. Dr. Wen is an emergency physician at George Washington University and author of “When Doctors Don’t Listen: How to Avoid Misdiagnoses and Unnecessary Tests.”

    “Sound Medicine” covers controversial ethics topics, breakthrough research studies and the day-to-day application of recent advancements in medicine. It’s also available via podcast and Stitcher Radio for mobile phones and iPads and posts updates on Facebook and Twitter. 

    Co-produced by the IU School of Medicine and WFYI Public Radio (90.1 FM) and underwritten in part by Indiana University-Purdue University Indianapolis, “Sound Medicine” airs on the following Indiana public radio stations: WBSB (Anderson, 89.5 FM), WFIU (Bloomington, 103.7 FM; Columbus, 100.7 FM; Kokomo, 106.1 FM; Terre Haute, 95.1 FM), WNDY (Crawfordsville, 91.3 FM), WVPE (Elkhart/South Bend, 88.1 FM), WNIN (Evansville, 88.3 FM), WBOI (Fort Wayne, 89.1 FM), WFCI (Franklin, 89.5 FM), WBSH (Hagerstown/New Castle, 91.1 FM), WFYI (Indianapolis), WBSW (Marion, 90.9 FM), WBST (Muncie, 92.1 FM), WBSJ (Portland, 91.7 FM), WLPR (Lake County, 89.1 FM) and WBAA (West Lafayette, 101.3 FM).

    “Sound Medicine” is also broadcast on these public radio stations across the country: KSKA (Anchorage, Alaska), KTNA (Talkeetna, Alaska), KUHB (Pribilof Islands, Alaska), KUAF (Fayetteville and Fort Smith, Ark.), KIDE (Hoopa Valley, Calif.), KRCC (Colorado Springs, Colo.), KEDM (Monroe, La.), WCMU (Mount Pleasant, Mich.), WCNY and WRVO-1 (Syracuse, N.Y.), KMHA (Four Bears, N.D.), WYSU (Youngstown, Ohio), KPOV (Bend, Ore.), KEOS (College Station, Texas), HPPR (High Plains Public Radio), which includes: KCSE (Lamar, Col.), KZNK (Brewster, Kan.), KZCK (Colby, Kan.), KZNZ (Elkhart, Kan.), KZAN (Hays, Kan.), KZNA (Hill City, Kan.), KGUY (Guymon, Okla.), KJJP (Amarillo, Texas), KTXP (Bushland, Texas), KTDH (Dalhart, Texas), KTOT (Spearman-Perryton, Texas).

    Please check local listings for broadcast dates and times.

  • Leading gastrointestinal cancer expert joins IU Simon Cancer Center

    Leading gastrointestinal cancer expert joins IU Simon Cancer Center

    INDIANAPOLIS — A leading gastrointestinal cancer expert has joined the Indiana University Melvin and Bren Simon Cancer Center.

    Bert Howard O’Neil, M.D., has been named the inaugural Joseph W. and Jackie J. Cusick Professor of Oncology and a professor of medicine at the Indiana University School of Medicine. He is also the Phase I director and director of the gastrointestinal cancer research program at the IU Simon Cancer Center, and he will represent the  cancer center on the Big Ten Cancer Research Consortium steering committee.

    As the Phase I director, Dr. O’Neil will oversee clinical trials that are the necessary first step in testing a new cancer treatment in patients. Phase I studies test the best way to give a new treatment (for example, by mouth, intravenous infusion or injection) and the best dose.

    Although Dr. O’Neil will oversee the program for all areas of cancer treatment, his area of expertise is in gastrointestinal cancers, with a particular concentration on pancreas, colorectal and hepatocellular carcinomas, a type of liver tumor. He has considerable expertise in targeting new drugs to specific molecular targets on tumors. This therapeutic individualization, in which treatments are tailored to individual patients and their cancer’s unique “fingerprint,” is one of the most promising areas of cancer research.

    “Finding new and better agents to treat cancer, particularly gastrointestinal cancers, is a major focus of the IU Simon Cancer Center,” Patrick J. Loehrer, director of the IU Simon Cancer Center, said. “There is no one that I know in the country who is better suited for this role than Dr. O’Neil. He is the complete package as he’s both smart and dedicated.”

    Dr. O’Neil was most recently an associate professor of medicine and director of the gastrointestinal malignancies research program at the University of North Carolina at Chapel Hill. He also was the medical director of the UNC Lineberger Comprehensive Cancer Center’s clinical protocol office where he designed and conducted clinical and translational studies.

    He is a member of the American Association of Cancer Research and the American Society of Clinical Oncology.

    He is a section reviewer for the journal Gastrointestinal Malignancies and an ad hoc reviewer for the Journal of Clinical Oncology, Cancer, Oncology, Lancet Oncology, Gastroenterology, American Journal of Oncology and the Annals of Oncology, among others. He presents regularly at national scientific meetings.

    Dr. O’Neil earned his medical degree from the University of California, Los Angeles, and he completed his
    internal medicine residency and fellowship in hematology/oncology at the University of California, San Francisco.

    About the Cusick professorship

    The Cusick professorship was established by Jackie J. Cusick in memory of her husband Joseph, who co-founded, co-owned and co-operated NCA Group. He was instrumental in building New Hope Presbyterian Church in Fishers, Ind., and was interested in advancing educational opportunities. It is the intent of the donor that the holder be involved in clinical or basic science research aimed at enhancing treatment for patients with gastrointestinal cancers.