• Brown Center for Immunotherapy names Huda Salman, MD, PhD as inaugural executive director

    Brown Center for Immunotherapy names Huda Salman, MD, PhD as inaugural executive director

    INDIANAPOLIS—Indiana University School of Medicine has named its first executive director of the Brown Center for Immunotherapy. Huda Salman, MD, PhD will become the center’s new leader, effective November 1.

    Salman joins IU School of Medicine from Stony Brook University and Stony Brook Cancer Center where she is currently an associate professor, section chief of hematological malignancies and director of the CAR T-cell program. She founded the hematological malignancies section as well as the Cancer Center Adolescence and Young Adult Program at Stony Brook. She completed a fellowship in hematology/oncology at Albert Einstein College of Medicine, residency at Cornell Medical College and medical school at Jordan University. A leukemia survivor herself, Salman’s clinical expertise is focused on hematological malignancies and bone marrow transplantation and cellular therapy, particularly for acute and aggressive lymphomas. Her most recent work on CAR T-cell and immunotherapy is extramurally funded and very well received in the medical community.

    At IU School of Medicine, Salman will hold the title of Don Brown Chair in Immunotherapy and professor of medicine in the Department of Medicine, Division of Hematology and Oncology.

    “I’m excited to join IU and focus on cancer immunology research and immunotherapy,” Salman said. “This is a great opportunity to establish new treatments through basic, translational and clinical research in collaboration with other IU faculty and existing programs as well as across the country. I’m also looking forward to building a dedicated team of scientists and clinicians to advance the field in this area of medicine.”

    The Brown Center for Immunotherapy was established in 2016 thanks to a $30 million gift from Indianapolis entrepreneur Donald E. Brown, MD. The center studies new ways to deploy immune-based therapies to treat cancer and pioneer use of technology in other diseases. Currently, researchers are focused on a technology known as chimeric antigen receptor-modified T-cells, or CAR T-cells. T-cells are important cells in the body’s immune system, but often cannot detect cancer cells due to the defenses put up by the malignant tumor cells. The immunotherapy approach is based on harnessing the immune system to fight cancer cells. In CAR T-cell therapy, the patient’s T-cells are collected, genetically re-programmed to more efficiently identify and attack cancer cells, then re-infused back into the patient.

    “Immunotherapy represents one of the most promising advances in recent decades, if not in the entire history of medicine,” said Jay L. Hess, MD, PhD, MHSA, executive vice president for university clinical affairs and IU School of Medicine dean. “We are excited to welcome Dr. Salman as the Brown Center’s inaugural director and look forward to the new advancements the center will make under her leadership.”

    The center is part of the IU Melvin and Bren Simon Comprehensive Cancer Center, a National Cancer Institute-designated Comprehensive Cancer Center with more than 250 investigators who work to develop better approaches to prevention, diagnosis and treatment of cancer. The Brown Center also collaborates with the private sector throughout Central Indiana, including leaders in pharmaceuticals, biotechnology and other relevant fields.

    “Dr. Salman will recruit and lead a team of scientists to improve the application of adult and pediatric cancer cell therapy and pioneer the use of this powerful technology for other diseases,” said Kelvin Lee, MD, director of the cancer center and associate dean for cancer research at IU School of Medicine. “With her years of expertise, we are confident that she will help the Brown Center continue its important work to develop methods to make this highly-specialized therapy more widely accessible to make the greatest impact on patients’ lives.”

    The Brown Center for Immunotherapy is focused on multiple myeloma and triple negative breast cancer, two diseases for which the School of Medicine and its clinical partner Indiana University Health have a strong foundation of talent, sizable patient populations and existing resources that can be leveraged to maximize impact. Researchers will also investigate potential opportunities to prevent and treat Alzheimer’s disease and other neurodegenerative disorders with immunotherapies.

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    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 unlocks new approach for possible pancreatic cancer treatment

    IU cancer researcher unlocks new approach for possible pancreatic cancer treatment

    INDIANAPOLIS—Researchers at the Indiana University Melvin and Bren Simon Comprehensive Cancer Center have identified how restoring a missing molecule in pancreatic fibrosis could help deliver treatments to cancer cells.

    Pancreatic cancer is one of the deadliest cancers with only 10.8 percent of people surviving five years after diagnosis. One risk factor for pancreatic cancer is chronic pancreatitis, a fibroinflammatory disease. In response to internal injury or damage, the body produces a fibrous connective tissue—much like scar tissue—in a process called fibrosis. Pancreatic fibrosis occurs in both pancreatic cancer and chronic pancreatitis.

    “These pancreatic cancer cells are very smart; they develop this thick, fibrotic tissue around the tumors. That poses a major barrier for the drug delivery when clinicians try to target these tumors because the therapies cannot penetrate these tumors,” said Janaiah Kota, PhD, assistant professor of medical and molecular genetics at IU School of Medicine and a researcher at the IU Simon Comprehensive Cancer Center.

    Kota and colleagues found that a molecule called microRNA-29a (miR-29a) functions as an anti-fibrosis and anti-inflammatory in the pancreas. Using this molecule in drug therapy could help stop fibrosis so that treatments could reach the cancer cells. Currently, there are no FDA-approved therapies to reduce fibrosis.

    “This tiny molecule is missing in the pancreas and, more broadly, the fibrotic tissue. When we put this molecule back in cells, it significantly reduces the potential for cancer cells to develop fibrotic tissue around the tumors,” Kota said.

    In findings published in JCI Insights, researchers established the role of miR-29a as a therapeutic agent in mouse models. Now Kota is developing methods to deliver the molecule back into the pancreas. He is using a pancreas targeted gene delivery approach called adeno-associated virus (AAV) space region therapy, which could carry the molecule directly to the pancreas.

    “When we delete the molecule in mouse models with pancreatitis, they develop a significant fibrosis and inflammation, mimicking the human disease,” said Kota, senior author on the study. “This is providing compelling evidence for us to use this molecule as a potential therapeutic agent both in cancer patients as well as in pancreatitis patients.”

    “The study of pancreatic fibrosis serves an unmet clinical need as there is currently no FDA-approved drug which might halt or reverse this process. This patient population is at high risk for developing pancreas cancer, and potentially stopping or reversing the fibrosis may reduce this risk. Physicians worldwide continue to struggle with management of patients with chronic pancreatitis and pancreas cancer. We are optimistic that miR-29a has the potential to fill an important gap and reduce pancreatic fibrosis, with a broader application for other fibrotic diseases,” said Evan Fogel, MD, a cancer center researcher and co-author on the publication. Fogel is also a professor of medicine in the IU School of Medicine Department of Medicine.

    Future therapies for chronic pancreatitis could potentially prevent those patients from developing pancreatic cancer. Additionally, the development of an anti-fibrotic therapy could have applications beyond the pancreas. Fibrosis also causes complications in lung and liver diseases.

    First author Shatovisha Dey, PhD, is a post-doctoral fellow at IU School of Medicine. In addition to Kota, Fogel and Dey, authors include Jeffrey J. Easler, MD, Lata M. Udari, Primavera Rivera Hernandez, MS, Jason J. Kwon, PhD, from IU School of Medicine; Brandon Wills from the University of California; Stephen Pandol, MD, from Cedar-Sinai Medical Center.

    This research was funded in part by the American Cancer Society Research Scholar Grant, Indiana Clinical and Translational Sciences Institute (UL1TR001108), and the IU Simon Comprehensive Cancer Center (P30CA082709).

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    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 receives $2.5 million grant to develop lung cancer treatment

    IU cancer researcher receives $2.5 million grant to develop lung cancer treatment

    INDIANAPOLIS—A researcher at the Indiana University Melvin and Bren Simon Comprehensive Cancer Center received a five-year, $2.5 million grant from the National Cancer Institute to develop a novel therapy to treat lung cancer.

    The research led by John Turchi, PhD, uses a small drug-like molecule designed to disrupt the DNA repair pathways that allow lung cancer cells to continue replicating and tumors to grow. Turchi is the Tom and Julie Wood Family Foundation Professor of Lung Cancer Research at Indiana University School of Medicine.

    The body repairs DNA damage daily from things such as UV rays from the sun, toxins in the air, and chemicals from cigarettes. Turchi researches a protein called replication protein A (RPA), which binds to single-strand DNA to signal DNA damage response (DDR) to repair the damage and make new cells.

    “The novel therapeutics we are developing would treat patients who often have limited therapeutic options, which include smoking-induced lung cancers,” Turchi said. “We think this group of patients could benefit from what we’ve learned over the last 30 years from our understanding of this pathway.”

    Lung cancer is the leading cause of cancer death in men and women and accounts for more than 20 percent of all cancer deaths. Cancer cells divide more rapidly than normal cells, putting them under replication stress. The cancer cells rely on the DNA damage response to ensure they can continue to divide and thrive. And that’s what Turchi wants to exploit to stop cancer.

    “When we can inhibit replication protein A from binding to single-stranded DNA during this replication stress, we can induce massive cell death—and that’s specific to cancer, which gives us our therapeutic window,” Turchi said.

    The RPA inhibitor developed by IU researchers targets cancer through a different mechanism from other cancer therapies. RPA binds to damaged DNA like a flashing light to signal it needs to be repaired. The RPA inhibitor stops that signal, so the cells die.

    In addition to applications for lung cancer, Turchi’s research team is exploring the RPA inhibitor to treat ovarian cancer. Lung and ovarian cancers are both marked by many mutations in the DNA damage response pathway.

    Turchi’s lab is now working to move findings from the cancer research lab to patients in the clinic based on decades of research into these pathways.

    “We are now to the point where our work is less of the discovery and more of the implementation and translational work that is driven by clinical possibilities,” Turchi said.

    For this research, Turchi established new collaborations with cancer center researchers at core research facilities: Jun Wan, PhD, director of Cancer Bioinformatics Core; Karen Pollok, PhD, director of In Vivo Therapeutics Core; and Andi Masters, lab director of Clinical Pharmacology Analytical Core. Cancer center physician-scientists Shadia Jalal, MD, and Catherine Sears, MD, are providing vital clinical perspectives as the research team moves toward clinical applications.

    “The complementary expertise of the many cancer center researchers is going to allow us to answer some really important questions and ultimately impact patients’ lives,” he said.

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    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 School of Medicine research team discovers drug target, pathway for treating muscle and fat wasting in pancreatic cancer patients

    IU School of Medicine research team discovers drug target, pathway for treating muscle and fat wasting in pancreatic cancer patients

    INDIANAPOLIS—A team of all Indiana University School of Medicine researchers have discovered a novel drug target to treat involuntary muscle and fat wasting – known as cachexia - in people with pancreatic cancer. They’ve also identified the way muscle and fat are communicating with one another in the presence of a pancreatic tumor, which could prove important to extending overall pancreatic cancer patient survival in those suffering from cachexia. Their findings were recently published in the Journal of Experimental Medicine, a scientific journal focused on publishing outstanding studies in medical biology. 

    Pancreatic cancer is one of the deadliest cancers, with only a 10% survival rate beyond five years. Alex Trebek, host of popular TV show "Jeopardy, was diagnosed with stage four pancreatic cancer. He lived for two years following his diagnosis. Pancreatic cancer patients experience some of the highest rates of cachexia at 85%. Cachexia causes morbidity, treatment toxicity and low quality of life. Moreover, researchers estimate cachexia is the cause of death in more than a third of all patients with any type of cancer.

    Interleukin 6, more commonly referred to as “IL-6” is a protein in the human body, which is necessary for maintaining good overall health. However, when overexpressed it’s known to be associated with cachexia.  The role of IL-6 expressed from tumor cells was unknown until now. 

    "We took the path less traveled," said Joe Rupert, PhD, Biochemistry and Molecular Biology and lead author of the study. “Broadly, a tumor includes two types of compartments; stromal and epithelial. While a lot of research has been done on the idea that the stromal cells are producing IL-6, we focused instead on the epithelial cells. When we removed IL-6 from the tumor’s epithelial cells, significantly less fat and muscle wasting occurred and overall survival increased.” 

    The research team also discovered the fat and muscle are talking with one another. And, when the researchers deleted IL-6 from the tumor, the cross-talk was greatly diminished.

    “We found that tumor-derived IL-6 in turn induced IL-6 expression in fat and IL-6 receptor expression in muscle, resulting in a feed-forward vicious cycle of IL-6 trans-signaling leading to fat and muscle wasting”,  said Teresa Zimmers, PhD, H.H. Gregg Professor of Cancer Research and Professor of Surgery at IU School of Medicine and senior author of the study. “We believe that if you can stop this crosstalk you can block cachexia and increase survival.”

    The team also discovered lipid accumulation increases in muscle with cachexia. 

    “Increases in IL-6 signaling largely increases fat wasting, which dumps lipids and fatty acids into blood that the muscle picks up, leading it to become overloaded. This increases muscle stress and promotes more muscle wasting,” said Rupert.

    Going forward, the team is investigating several approaches to stopping the crosstalk among fat and muscle through lipid and IL-6 neutralization. 

    This research was funded in part by grants from the National Institutes of Health (grants R01CA122596, R01CA194593, and R01GM137656), the Indiana University Melvin and Bren Simon Comprehensive Cancer Center, Lilly Endowment, the Bioinformatics analysis was supported by the Purdue University Center for Cancer Research (grant P30CA023168), the Walther Cancer Foundation, and the Indiana University (IU) Melvin and Bren Simon Comprehensive Cancer Center (grant P30CA082709), the last of which also supports the IU Melvin and Bren Simon Comprehensive Cancer Center Tissue Procurement and Distribution Core, In Vivo Therapeutics Core, Flow Cytometry Core, and Genomics Core. 

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

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    About IU School of Medicine
    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 School of Medicine researchers develop computer program to predict whether patients could be at high risk for Alzheimer’s and cancer

    IU School of Medicine researchers develop computer program to predict whether patients could be at high risk for Alzheimer’s and cancer

    INDIANAPOLIS—A group of researchers from Indiana University School of Medicine and Indiana University Bloomington have developed a program called Multi-Omics Graph cOnvolutional NETworks (MOGONET) that integrates omics data – such as DNA, RNA and proteins – to help researchers get a comprehensive understanding of human diseases. MOGONET can identify potential biomarkers for Alzheimer’s disease and cancers from the various omics data to predict which individuals may be at higher risk. 

    An article about MOGONET published this month in the scientific journal, Nature Communications, includes contributions from a multidisciplinary team of researchers including senior author Kun Huang, PhD, Assistant Dean for Data Sciences and professor of biostatistics and health data sciences at IU School of Medicine; co-corresponding author Zhengming Ding, assistant professor of computer science at Tulane University; first author Tongxin Wang, a computer science graduate student at Indiana University Bloomington, and others with expertise in medicine, computer science, electrical and computer engineering, and medical and molecular genetics. 

    “If we put all the data together, we can learn more about the underlying biological processes and the disease outcomes,” said Huang, who is also the Director of Data Science and Informatics for the IU Grand Challenge Precision Health Initiative, a program with bold goals to develop treatments for triple negative breast cancer, as well as to prevent Alzheimer’s disease. “We can also identify potential biomarkers that can separate individuals based on their outcomes. With precision medicine, when we look at one disease, there could actually be multiple subtypes. Those subtypes may require different treatment and may have different outcomes, so we are working to identify those subtypes by looking more holistically at multi-omics data.”

    Since it can be difficult to make meaningful statistical conclusions when working with multiple kinds of data, MOGONET utilizes graphs, which help show how the biomedical data are connected and interact with each other. The graph is created by using a combination of knowledge and data processing, then updated with the algorithm developed by artificial intelligence.

    “The graphs are specifically useful when we are looking at the relationships of large numbers of genes, proteins or microRNAs,” said Huang, who is also a research scientist at Regenstrief Institute. “The graphs give us a way to link those molecules and put them into a network structure, which is crucial for effective deep learning. Then if we see a good performance in the prediction, we can go back to determine which biomarkers are important.”

    Huang and his colleagues have demonstrated the capabilities and versatility of MOGONET through a wide range of biomedical applications, including Alzheimer’s disease patient classification, tumor grade classification in low-grade glioma (LGG), kidney cancer type classification, and breast invasive carcinoma subtype classification. 

    “In the future, we hope to be able to use blood or find less invasive ways to determine a patient’s risk,” said Huang, who is also the Associate Director of Data Science at IU Simon Comprehensive Cancer Center.

    By doing a deeper dive through the data, Huang says he and his colleagues can look for genes that may be potentially tractable for future use. That includes developing those genes as potential therapeutic targets, which is something they are already exploring with the IU School of Medicine-Purdue University Center for TaRget Enablement to Advance Therapeutics for Alzheimer’s Disease (TREAT-AD)

    This research was supported by the Indiana University Grand Challenge Precision Health Initiative, as well as National Institutes of Health grants R01EB025018 and U54AG065181. 

    Contact: Anna Carrera, acarrer@iu.edu, 614-570-6503 (cell)

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    About IU School of Medicine

    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 joins call for urgent action to get cancer-preventing HPV vaccination back on track

    Cancer center joins call for urgent action to get cancer-preventing HPV vaccination back on track

    The COVID-19 pandemic has interrupted delivery of key health services for children and adolescents, including HPV vaccination for cancer prevention

    INDIANAPOLIS—Indiana University Melvin and Bren Simon Comprehensive Cancer Center has joined National Cancer Institute (NCI)-designated cancer centers and other organizations in a joint statement urging the nation’s health care systems, physicians, parents and children, and young adults to get the human papillomavirus (HPV) vaccination back on track.

    Dramatic drops in annual well visits and immunizations during the COVID-19 pandemic have caused a significant vaccination gap and lag in vital preventive services among U.S. children and adolescents—especially  for the HPV vaccine. The pandemic also has exacerbated health disparities, leaving Black, Indigenous and other people of color; rural; and sexual minority adolescents at even greater risk for missed doses of this cancer prevention vaccine.

    Nearly 80 million Americans – 1 out of every 4 people – are infected with HPV, a virus that causes six types of cancers. Of those millions, nearly 36,000 will be diagnosed with an HPV-related cancer this year.

    Despite those staggering figures and the availability of a vaccine to prevent HPV infections, HPV vaccination     rates remain significantly lower than other recommended adolescent vaccines in the United States. Even before the COVID-19 pandemic, HPV vaccination rates lagged far behind other routinely recommended vaccines and other countries’ HPV vaccination rates. According to 2019 data from the Centers for Disease Control and Prevention (CDC), just more than half (54%) of adolescents were up to date on the HPV vaccine.

    Those numbers have declined dangerously since the pandemic.

    • Early in the pandemic, HPV vaccination rates among adolescents fell by 75%, resulting in a large cohort of unvaccinated children.
    • Since March 2020, an estimated one million doses of HPV vaccine have been missed by adolescents  with public insurance—a decline of 21% over pre-pandemic levels.
    • Adolescents with private insurance may be missing hundreds of thousands of doses of HPV vaccine.

    "Due to the COVID-19 pandemic, many adolescents have fallen behind with their routinely recommended vaccines, particularly HPV vaccine," Gregory Zimet, PhD, professor of pediatrics at IU School of Medicine and a researcher at IU Simon Comprehensive Cancer Center, said. "Earlier in the pandemic, parents were reluctant to bring their adolescents to health clinics and doctors’ offices for immunizations. However, now is the time to get back on track as a nation and in Indiana with adolescent vaccination to ensure we protect our youth and our communities."

    The United States has recommended routine HPV vaccination for females since 2006 and for males since 2011. Current recommendations are for routine vaccination at ages 11 or 12 or starting at age 9. Catch-up HPV vaccination is recommended through age 26. Adults aged 27 through 45 should talk with their health care providers about HPV vaccination because some people who have not been vaccinated might benefit. The HPV vaccine series is two doses for children who get the first dose at ages 9 through 14 and three doses for those who get the first dose at ages 15 and older and for immunocompromised people.

    NCI cancer centers strongly encourage parents to vaccinate their adolescents as soon as possible. The CDC recently authorized COVID-19 vaccination for 12- to 15-year-old children allowing for missed doses of routinely recommended vaccines, including HPV, to be administered at the same time. NCI cancer centers strongly urge action by health care systems and providers to identify and contact adolescents due for vaccinations and to use every opportunity to encourage and complete vaccination.

    "HPV vaccination is cancer prevention. By catching up on missed doses of HPV vaccine now, we will protect our adolescents from serious diseases, including cervical and head and neck cancers. Vaccinating our adolescents against COVID-19, now available for ages 12 years and older, is a reminder to ensure that they are also protected from HPV through vaccination," Zimet, also co-director of the IUPUI Center for HPV Research, said.

    More information on HPV is available from the CDC and National HPV Vaccination Roundtable. This is the fourth time that all NCI-designated cancer centers have come together to issue a national call to action. All 71 cancer centers unanimously share the goal of sending a powerful message to health care systems, physicians, parents and children, and young adults about the importance of HPV vaccination for the elimination of HPV-related cancers.

    Organizations endorsing this statement include the Association of American Cancer Institutes; American Association for Cancer Research; American Cancer Society; American Society of Clinical Oncology; American Society of Pediatric Hematology/Oncology; American Society of Preventive Oncology; and the Prevent Cancer Foundation. 

    Contact: Michael Schug, maschug@iu.edu 

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    About IU School of Medicine

    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 researchers study cognitive dysfunction after chemotherapy

    Cancer researchers study cognitive dysfunction after chemotherapy

    PITTSBURGH/INDIANAPOLIS—Cancer researchers at Indiana University and the University of Pittsburgh received a five-year, $3 million grant from the National Cancer Institute (NCI) to study cognitive dysfunction after chemotherapy. 

    Following chemotherapy, survivors often find it more challenging to learn new tasks, remember words or do things as efficiently or quickly as they once did. That’s why Robert Ferguson, PhD, a clinical psychologist in the Behavioral Cancer Control Program at UPMC Hillman Cancer Center, developed a cognitive behavioral therapy called Memory and Attention Adaptation Training, or MAAT, which will be the focus of the first large-scale, multi-center study thanks to the new grant. 

    Ferguson is collaborating with Brenna McDonald, PsyD, a member of the Cancer Prevention and Control research program at the Indiana University Melvin and Bren Simon Comprehensive Cancer Center, to test MAAT and supportive therapy to determine the effects of both on improving memory problems and emotional resilience among breast cancer survivors.

    MAAT is cognitive behavioral therapy in which survivors work with a psychologist to identify specific situations at home or on the job where memory problems are likely to occur and to learn specific strategies to address those issues. In supportive therapy, survivors also work with the psychologist, but they explore emotional strengths and build resilience in coping with memory problems and cancer survivorship in general. Both therapies consist of eight telehealth visits of 45-minutes each.

    “The survivor and therapist review what is currently known – and not known – about memory problems associated with cancer and cancer treatment,” said Ferguson, an assistant professor of hematology/oncology in Pitt’s School of Medicine. “They also address distress and aggravation that can accompany memory difficulty in daily life to identify the specific situations and apply strategies to reduce or mitigate memory problems.”

    Participants will learn to recognize that everyone at some point forgets something, said McDonald, professor of radiology and imaging sciences at IU School of Medicine. 

    “We all sometimes forget something, such as why we walked into a room. And that's OK. We know, however, that patients are quick to attribute that to their treatment, which makes them feel helpless,” she said.

    Both therapies have been designed and tested as a telehealth-delivered therapy to reduce travel and time burdens on survivors and families. While it can be delivered in-office, too, many survivors have exhausted their paid time off work and may have used much of their savings to help pay for cancer treatment, so the telehealth option is often preferred.

    With the latest grant, the researchers will look at the functional MRI of participants to evaluate underlying changes in brain activation patterns that are believed to be associated with treatment. In previous research, McDonald and Ferguson have demonstrated enhanced working memory following treatment among individuals with traumatic brain injury.

    The two researchers are building on a collaboration that started when they were both faculty at Dartmouth College nearly two decades ago. They conducted small clinical trials and pilot studies on the cognitive symptoms in breast cancer patients, which led to the development of MAAT.  

    Pitt and IU each hope to evaluate 100 women, half of whom will receive MAAT while the others receive the supportive therapy. 

    For more information visit: https://hillmanresearch.upmc.edu/telehealth-and-memory-study/.

    Contact: Michael Schug, maschug@iu.edu, 317-417-0709

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    About IU School of Medicine
    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.

    About the IU Simon Comprehensive Cancer Center
    The Indiana University Melvin and Bren Simon Comprehensive Cancer Center, one of only 51 National Cancer Institute (NCI)-designated Comprehensive Cancer Centers in the nation, is home to the cure of testicular cancer and the world’s only healthy breast tissue bank. The prestigious NCI comprehensive designation recognizes the center’s excellence in basic, clinical, and population research, outstanding educational activities, and effective community outreach program across the state. The center’s physician-scientists have made protocol-defining discoveries that have changed the way doctors treat numerous forms of cancer. 

  • IU School of Medicine researchers discover gamechanger combination drug for triple negative breast cancer

    IU School of Medicine researchers discover gamechanger combination drug for triple negative breast cancer

    A team of Indiana University School of Medicine researchers has developed a novel antibody-drug conjugate for treating triple negative breast cancer. The study, led by senior author Xiongbin Lu, PhD, Vera Bradley Foundation Professor of Breast Cancer Innovation at IU School of Medicine, has been published in the prestigious interdisciplinary medical journal, Science Translational Medicine

    Triple negative breast cancer accounts for about 15 percent of all breast cancer cases. When a patient tests negative for estrogen receptors, progesterone receptors and has low levels of a protein called HER2, the patient is considered to have “triple negative” breast cancer. Patients with triple negative breast cancer typically have the poorest prognosis because there are not very many treatment options.

    All breast cancers are often missing a chromosome fragment known as 17p, which contains genes that can help your body suppress cancerous tumors.

    Lu and his team combined trastuzumab—a targeted cancer drug for HER2-positive breast cancer patients—with α-amanitin, a small-molecule inhibitor which is originally isolated from a toxic mushroom, to create a novel drug called T-Ama. Even though historically trastuzumab has not been effective at targeting tumors for triple negative breast cancer patients by itself, Lu and his team found that T-Ama was effective at killing breast cancer cells with low HER2 levels in animal models during their study. They also determined that the loss of chromosome 17p makes the tumor cells more likely to respond to α-amanitin. 

    “Our big question was whether we could find a new drug which can efficiently kill cancer cells and also enhance the immune response of tumors to cancer immunotherapy,” said Lu, who is also a researcher at the Indiana University Melvin and Bren Simon Comprehensive Cancer Center. “Our work aims to fulfill both of those.” 

    While the chromosome 17p loss can promote breast tumor growth, Lu said it also opens up opportunities to develop precision immunotherapy targeted to that area. Lu said the safety and efficacy of T-Ama has already been validated, so their next step will be a clinical study for humans. Lu and one of his postdoctoral fellows have already been awarded the U.S. patent for T-Ama. 

    “The drug will be able to be used alone or in combination with current immune checkpoint inhibitors,” said Lu. “I think it will be a gamechanger for the field of triple negative breast cancer therapy.” 
  • IU cancer center researchers discover how breast cancer cells hide from immune attack

    IU cancer center researchers discover how breast cancer cells hide from immune attack

    INDIANAPOLIS—Researchers at the Indiana University Melvin and Bren Simon Comprehensive Cancer Center have identified how breast cancer cells hide from immune cells to stay alive. The discovery could lead to better immunotherapy treatment for patients.

    Xinna Zhang, PhD, and colleagues found that when breast cancer cells have an increased level of a protein called MAL2 on the cell surface, the cancer cells can evade immune attacks and continue to grow. The findings are published this month in The Journal of Clinical Investigation and featured on the journal’s cover.

    cover of the journal of clinical investigation

    “Like other cancer cells, breast cancer cells present tumor-specific antigens on the cell membrane, which immune cells recognize so they can kill the tumor cells,” Zhang said. “But our study found that MAL2 can reduce the level of these antigens, so these tumor cells are protected and can no longer be recognized as a threat by these immune cells.”

    The lead author of the study, Zhang is a member of the IU Simon Comprehensive Cancer Center and assistant professor of medical and molecular genetics at IU School of Medicine.

    Considered the future of cancer treatment, immunotherapy harnesses the body’s immune system to target and destroy cancer cells. Understanding how cancer cells avoid immune attacks could offer new ways to improve immunotherapy for patients, explained Xiongbin Lu, PhD, Vera Bradley Foundation Professor of Breast Cancer Innovation and cancer center researcher. 

    “Current cancer immunotherapy has wonderful results in some patients, but more than 70% of breast cancer patients do not respond to cancer immunotherapy,” Lu said. “One of the biggest reasons is that tumors develop a mechanism to evade the immune attacks.”

    The collaborative research team set out to answer key questions: How do breast cancer cells develop this immune evasion mechanism, and could targeting that action lead to improved immunotherapies?

    Zhang and Lu, members of the Vera Bradley Foundation Center for Breast Cancer Research, turned to biomedical data researcher Chi Zhang, PhD, assistant professor of medical and molecular genetics at IU School of Medicine. Chi Zhang developed a computational method to analyze data sets from more than 1,000 breast cancer patients through The Cancer Genome Atlas. That analysis led researchers to MAL2; it showed that higher levels of MAL2 in breast cancer, and especially in triple-negative breast cancer (TNBC), was linked to poorer patient survival.

    “Dr. Chi Zhang used his advanced computational tool to build a bridge that connects cancer genetics and cancer genomics with a clinical outcome,” Lu said. “We can analyze molecular features from thousands of breast tumor samples to identify potential targets for cancer immunotherapy. From that data, MAL2 was the top-ranked gene that we wanted to study.”

    Xinna Zhang took that data to her lab to determine MAL2’s purpose in the cells, how it affects breast cancer cell growth and how it interacts with immune cells. Using breast cancer tissue samples from IU patients, cell models and animal models, she found that breast cancer cells express more MAL2 than normal cells. She also discovered that high levels of MAL2 significantly enhanced tumor growth, while inhibiting the protein can almost completely stop tumor growth.

    In Lu’s lab, he used a three-dimensional, patient-derived model called an organoid to better understand how reducing MAL2 could improve patient outcomes.

    “Tumor cells can evade immune attacks; with less MAL2, the cancer cells can be recognized and killed by the immune system,” Lu said. “MAL2 is a novel target. By identifying its function in cancer cells and cancer immunology, we now know its potential as a cancer immunology target.”

    Researchers now are exploring ways these findings could be used to develop and improve breast cancer therapies.

    Lu is co-leading a cancer immunotherapy program for triple negative breast cancer as part of the Indiana University Precision Health Initiative. Both Xinna Zhang and Chi Zhang are also involved in the initiative for developing novel breast cancer immunotherapy. The Precision Health Initiative, the first recipient of funding from the Indiana University Grand Challenges Program, is enhancing the prevention, treatment, and health outcomes of human diseases through a more precise analysis of genetic, developmental, behavioral and environmental factors that shape an individual’s health.

    Additional authors are Bryan P. Schneider, MD, Yunlong Liu, PhD, and Sha Cao, PhD, of IU Simon Comprehensive Cancer Center; Yuanzhang Fang, PhD, Lifei Wang, Changlin Wan, Yifan Sun, Kevin Van der Jeught, PhD, Zhuolong Zhou, PhD, Tianhan Dong, Ka Man So, Tao Yu, PhD, Yujing Li, PhD, Haniyeh Eyvani, Austyn B. Colter, Edward Dong, George E. Sandusky, PhD, of IU School of Medicine; and Jin Wang, PhD, of Baylor College of Medicine.

    This study was supported by the Vera Bradley Foundation for Breast Cancer Research, the American Cancer Society Institutional Research Grant, and the National Institutes of Health (R01CA203737 and R01CA206366).

    Contact: Candace Gwaltney, cmgwaltn@iu.edu

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    About IU School of Medicine

    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 center findings could reduce treatment-related complication for blood cancer patients

    IU cancer center findings could reduce treatment-related complication for blood cancer patients

    INDIANAPOLIS— Researchers at the Indiana University Melvin and Bren Simon Comprehensive Cancer Center published promising findings today in the New England Journal of Medicine on preventing a common complication to lifesaving blood stem cell transplantation in leukemia.

    Sherif Farag, MD, PhD, found that using a drug approved for Type 2 diabetes reduces the risk of acute graft-versus-host disease (GVHD), one of the most serious complications of blood stem cell transplantation. GVHD occurs in more than 30 percent of patients and can lead to severe side effects and potentially fatal results. Farag is the Lawrence H. Einhorn Professor of Oncology and professor of medicine at IU School of Medicine, a member of the IU Simon Comprehensive Cancer Center and program and medical director of the hematological malignancies and bone marrow and blood stem cell transplantation at IU Health.

    In the IU clinical study, blood stem cell transplant patients received the oral drug called sitagliptin. Acute GVHD occurred in only two of 36 patients within 100 days of their transplant. The 5 percent occurrence represents a drastic reduction of GVHD, which studies have found can affect 34 percent to 51 percent of patients in the first three months after transplant. 

    Graft-versus-host disease occurs when the donated blood stem cells (the graft) attack the transplant recipient’s (the host) tissue. 

    “The rate looks very encouraging and it’s achieved with a very simple and relatively inexpensive intervention of sitagliptin,” Farag said. “This result is significant and offers a new approach and a new target for inhibition of graft-versus-host disease. We achieved a much lower rate than we could have hoped.” 

    Sitagliptin targets an enzyme called dipeptidyl peptidase-4 (DPP-4), which is involved in a variety of processes in the body. It is used for Type 2 diabetes to improve insulin secretion and glucose control. 

    Hal Broxmeyer, PhD, a pioneer in the field of umbilical cord blood stem cell transplantation and distinguished professor at IU School of Medicine and a co-author with Farag, previously found that DPP-4 regulates blood cell production and explored if taking sitagliptin would improve engraftment for cord blood transplants. While there seemed to be some improvement in engraftment of cord blood transplants, one striking finding was the patients had a much lower rate of acute graft-versus-host disease than expected. Farag’s lab took on that data and found targeting DPP-4 with sitagliptin inhibits the immune T cell activation that leads to GVHD. 

    Farag noted that repurposing sitagliptin offers a relatively inexpensive and accessible approach to preventing GVHD. 

    “These findings are very significant because there are a lot of other different drugs that are being tested, including ones that are very expensive or require administration intravenously for a prolonged time well beyond the time of recovery and transplant,” Farag said.

    Patients in the study were ages 18 to 60 and had one of the following blood cancer or diseases: acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia or myelodysplastic syndrome. The patients in the study received sitagliptin orally one day before their transplant and the day of their transplant, plus 14 days after their transplant. 

    Patients in the study did not face any unexpected or unusual toxicities or higher relapse rates than what’s expected post-transplant.

    “This is a drug that is used to treat diabetes, and we're using it at a much higher dose. We asked if we are going to cause people to have low blood sugar or hypoglycemia—and we didn't find that,” Farag said. “As long as it's not combined with other drugs that lower the blood glucose in non-diabetic patients, it doesn't do that; we certainly confirm that in our findings.”

    Farag’s findings now need to be confirmed with a larger, multi-center randomized study. He also hopes to explore combination therapies with sitagliptin and if it could prevent chronic graft-versus-host disease.

    Additional authors from the cancer center are Mohammad Abu Zaid, MD, Jennifer E. Schwartz, MD, Rafat Abonour, MD, Michael J. Robertson, MD, and Ann J. Blakley, BS, as well as Teresa C. Thakrar, PharmD, of IU Health and Shuhong Zhang, PhD, of IU School of Medicine.

    This study was supported by grants from the National Heart, Blood, and Lung Institute of the National Institutes of Health (R01 HL112669 and R35 HL139599) and the IU Simon Comprehensive Cancer Center.

    Contact: Candace Gwaltney, cmgwaltn@iu.edu

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    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.