• Researchers make important new findings about how to test cancer-fighting drugs

    Researchers make important new findings about how to test cancer-fighting drugs

    INDIANAPOLIS—Researchers from Indiana University School of Medicine are discovering new ways to find out how effective a drug might be against cancer. Their findings are detailed in a new paper published by Science Advances.

    “This paper completely changes the way we need to collect tumor tissues and test for drug sensitivity,” said Harikrishna Nakshatri, PhD, a senior author of the paper. Nakshatri is the Marian J. Morrison professor of breast cancer research at IU School of Medicine and a researcher with the Vera Bradley Foundation Center for Breast Cancer Research at the Indiana University Melvin and Bren Simon Comprehensive Cancer Center. Hal Broxmeyer, PhD, a distinguished professor at IU School of Medicine who passed away in December 2021, also contributed to this study.

    Typically, tumors are collected and exposed to room oxygen, which is about 21 percent. However, different organs in the body have different oxygen levels. For example, the brain has 4.4 percent oxygen, blood 5.3 percent, and liver 5.4 percent. When cancer drugs are used on tumors in the clinical setting, they’re still in a patient’s body and are not exposed to ambient air.

    “The oxygen level in our different parts of the body is almost half of what we find in ambient air,” Nakshatri said. “Oxygen can have a different effect on the function of different proteins in the tumors. They may get activated, lose their activity level, get degraded or get stabilized. We wanted to test the tumors in a way that more closely resembles how they are in the body, so we know more about what drugs to use.”

    Researchers tested three different drugs on two different types of tumors. They split the tumors in half and tested one part in 5 percent oxygen, since that is an average oxygen level in the body, and exposed the other part to room oxygen before testing. They looked at the difference in the cancer stem cells, signaling pathways and how drugs behaved in the different oxygen levels. They found the sensitivy level of the tumor cells was different in 5 percent oxygen versus room oxygen.

    “This is a study that is now raising more questions we need to answer,” Nakshatri said. “Why do the cells react differently? Are we screening the drugs against cancer cells the right way? If we screen for drugs at the physiologic oxygen level, are we going to find different drugs that we may have missed all these years by doing the experiments at 21 percent oxygen?”

    In the future, researchers hope to study the different reactions tumors have to other various oxygen levels, like 1 percent or 20 percent. Nakshatri explained this kind of testing could act as another method of screening to determine a drug’s efficacy.

    “Suppose we identify a drug with the way we are doing right now in room oxygen, then add another layer of testing in the lab where we keep the cells at the physiologic oxygen level and compare whether the drug is working or not,” Nakshatri said. “If it works, then we can move forward to the clinical setting and it increases the chances of the drug being successful.”

    Other study authors from IU School of Medicine include Brijesh Kumar, PhD, Maegan Capitano, PhD, Yunlong Liu, PhD, Constance Temm, PhD, George Sandusky, PhD, and Amber Mosley, PhD. Read the full publication in Science Advances.

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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 provides advances in treatment of triple negative breast cancer

    IU School of Medicine research provides advances in treatment of triple negative breast cancer

    Findings published in influential Journal of Clinical Oncology

    INDIANAPOLIS – Indiana University School of Medicine physician scientist Bryan Schneider, MD is the principal investigator of clinical trial BRE12-158, a randomized clinical study published in the prominent Journal of Clinical Oncology the primary goal of which was to compare survival in women with high-risk (those who did not fully respond to chemotherapy prior to surgery) triple negative breast cancer (TNBC) with a genomically directed therapy versus standard of care.

    The study found that in the adjuvant (following chemotherapy and surgery) setting, a single genomically directed therapy was not better than a current standard of care option, which was capecitabine. 

    “Although this study did not prove genomically directed therapy was significantly superior alone, it did provide many advances for the treatment of high-risk triple negative breast cancer. We are thankful for the 200 patients and study teams across the United States who participated in this trial,” said Schneider, a researcher at the Vera Bradley Foundation Center for Breast Cancer Research at the IU Melvin and Bren Simon Comprehensive Cancer Center; also the location where the lab research portion of this study was conducted.

    Until 2015, no therapy, in the adjuvant setting had been shown to improve outcomes for patients with TNBC. This study showed that therapy (both the targeted therapy and the standard therapy option capecitabine) was markedly better than no therapy at all.  

    “Patients with high risk TNBC who received genomically targeted therapies had superior outcomes when compared with those who received no therapy. Additionally, patients who received capecitabine – a current standard of care option for TNBC – also had superior results when compared to those who received no therapy at all,” said Schneider, who is also the Vera Bradley Chair of Oncology at IU School of Medicine.

    Twenty percent of patients who were in the study did not receive therapy of any kind, in the adjuvant setting, for the treatment of their high risk TNBC. “We found that despite a study from 2015 which showed capecitabine was superior to receiving no therapy in patients with high risk TNBC, some were still receiving no therapy,” said Schneider. “When we observe a finding like this in a clinical study, experience shows us that in the real world, the numbers are actually much higher. Hopefully, these findings will further support that all patients with high risk TNBC in this setting will be considered for additional therapy as deemed appropriate by the treating oncologist. 

    This study also found that race did not appear to impact outcomes in this high-risk population. “This finding shows that the biology of TNBC is incredibly important and clinical trials should be focused in settings where disparate outcomes are most prevalent,” said Schneider. 

    Schneider also presented these findings as part of a spotlight session at the December 7-10, 2021 San Antonio Breast Cancer Symposium, an international scientific exchange among basic scientists and clinicians, working in breast cancer. 

    Clinical study BRE-158 has yielded an important discovery and provided valuable findings for oncologists and patients with triple negative breast cancer, said Tatiana Foroud, PhD, executive associate dean for research affairs at IU School of Medicine and leader of the IU Grand Challenge Precision Health Initiative. Results from this study, which are being published in prestigious journals read around the world, are doing what we promised to do, advance treatment options for patients with this terrible disease.”
     
    An initial discovery from clinical study BRE12-158  was published in JAMA Oncology. Schneider and his colleagues found that circulating tumor DNA (ctDNA) found in a patient’s blood, in the adjuvant setting, is a marker for residual disease; meaning patients who test positive for ctDNA are much more likely to have disease recurrence than those who test negative for ctDNA.

    “Circulating tumor DNA status remains a significant predictor of long-term outcomes in these patients,” said Schneider. It should be used to stratify patients in cancer clinical trials moving forward.”   

    The findings from BRE12-158 provided the needed rationale to launch the PERSEVERE  (BRE18-334) trial, which tests genomically targeted therapies in combination with capecitabine. PERSEVERE has now opened with four patients in the study. Using ctDNA technology, PERSEVERE is enrolling and following ctDNA-positive and negative patients. “Our hope is that these patients will continue to do well, enabling us to design future clinical trials of personalized therapy or no therapy that will further improve quality of life,” added Schneider.

    Study BRE12-158 was funded by the Vera Bradley Foundation for Breast Cancer in Roanoke and the Walther Cancer Center. BRE-158 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; Email: cldrury@iu.edu; Cellphone: 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 Simon Comprehensive Cancer Center enters into sponsorship with Indiana racing driver Jackson Lee

    IU Simon Comprehensive Cancer Center enters into sponsorship with Indiana racing driver Jackson Lee

    INDIANAPOLIS -- Marking 30 years of accelerating lifesaving research, the Indiana University Melvin and Bren Simon Comprehensive Cancer Center is putting the pedal to the metal through a new auto racing sponsorship. 

    The cancer center will join formula car driver Jackson Lee as the primary sponsor on his No. 2 Cape Motorsports entry in the 2022 Cooper Tires USF2000 championship. Jackson, a 19-year-old from Avon, Indiana, has been racing formula cars for four years, and will be starting as a freshman at IUPUI in 2022. He is entering his second season in USF2000, which is part of the Road to Indy, and races during INDYCAR weekend events at tracks around the country, including the Indianapolis Motor Speedway road course event in mid-May. 

    “We are excited to support Jackson and his team as there are many parallels between racing a car and racing to save lives,” Kelvin Lee, MD, cancer center director, explained. “When you watch a race team compete, you see the precision, determination and the science behind the sport. That’s a lot like cancer research and care.” (Note: Jackson Lee and Kelvin Lee have no familial relationship.)

    Through the sponsorship, Dr. Lee, who became cancer center director on Feb. 1, envisions connecting with the community to tout the cancer center’s research accomplishments that have benefited countless people over the last three decades.

    “I have quickly learned that Hoosiers are far too humble,” Dr. Lee said. “I am looking forward to this sponsorship allowing us to share just how much cancer expertise exists right here in Indiana.”

    IU’s physician-scientists have altered or defined treatment standards for such cancers as breast, pancreatic, thoracic, testis and colon as well as thymoma and thymic carcinoma and tumors associated with neurofibromatosis type 1, primarily in children, among others.   

    The IU Simon Comprehensive Cancer Center, which was established in 1992, serves as a central hub of cancer research across Indiana University. The center has more than 260 researchers who conduct all phases of cancer research, from laboratory studies to clinical trials to population-based studies that address environmental and behavioral factors that contribute to cancer. It is Indiana’s only Comprehensive Cancer Center designated by the National Cancer Institute, the nation’s top cancer agency, and one of only 51 in the nation to hold that status. 

    The prestigious designation recognizes its excellence in basic, clinical, and population research, its outstanding educational activities and effective community outreach program across the state.

    Dr. Lee also hopes that the year-long sponsorship will create opportunities for teambuilding within the cancer center. 

    “The cancer center is a large organization composed of laboratory scientists, physicians, nurses and support staff, among others,” Dr. Lee explained. “The pandemic has made it challenging to carry on our sense of community and camaraderie, so it’s my hope that we can all rally around Jackson’s team as we celebrate 30 years of improving the lives of cancer patients.”

    Like too many others, Jackson’s family has been impacted by cancer, as he lost his grandfather to lung cancer nearly two decades ago. 

    “Cancer has unfortunately impacted almost everyone’s family, mine included,” Jackson said. “I’ve enjoyed learning about the progress being made in cancer research and treatment, but there is much more that can be done. I’m excited to help in any way I can to encourage donations for research, raise awareness about the availability of the best treatment here in Central Indiana and to help celebrate the 30th anniversary of the cancer center at racetracks and other events throughout the year. I’m extremely grateful to the IU Simon Comprehensive Cancer Center for its support.”

    Jackson’s goal is to reach INDYCAR and the Indy 500 by at least 2026. Jackson won a karts to cars scholarship, has won four formula car races with 16 podiums (top-three finishes) and won a Team USA Scholarship in 2020 to race in several prestigious events in England.

    The 18-race 2022 USF2000 season begins Feb. 26 and 27 during the INDYCAR season opening weekend in St. Petersburg, Florida. 

    Media contact: Michael Schug; Email: 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

  • IU cancer researcher leads national work focused on developing treatments for inherited childhood cancers

    IU cancer researcher leads national work focused on developing treatments for inherited childhood cancers

    INDIANAPOLIS – An Indiana University cancer researcher is leading an $11.4 million grant from the National Cancer Institute in which he and others across the country will work on identifying new treatments for tumors that develop in children, adolescents and adults with a common genetic condition.

    First awarded in 2015 by the National Cancer Institute, the prestigious Specialized Programs of Research Excellence (SPORE) is led by D. Wade Clapp, MD. Clapp is chairman of the Department of Pediatrics at IU School of Medicine, the physician-in-chief at Riley Hospital for Children at Indiana University Health and a member of the IU Melvin and Bren Simon Comprehensive Cancer Center and the Herman B Wells Center for Pediatric Research. The project co-principal investigator is Kevin Shannon, MD, professor of pediatrics at the University of California, San Francisco (UCSF) and a member of the Helen Diller Family Comprehensive Cancer Center. 

    Clapp will lead the collaborative research effort to develop new treatments for tumors that develop in neurofibromatosis type 1 (NF1), the most common inherited syndrome causing a predisposition to cancer. It affects one in every 3,000 people worldwide, with about 100,000 individuals living with the syndrome in the United States. Individuals with NF1 have an increased risk of developing specific types of benign tumors and cancers including some brain tumors, a rare childhood leukemia and tumors that grow along the nerves and can progress to become sarcomas. 

    “Our SPORE grant is distinguished by its strong childhood cancer focus and multi-institutional effort, which brings together a coalition of the best NF1 investigators in the United States and likely the world,” Clapp said. “The grant involves six major institutions and the Pediatric Oncology Branch of the National Cancer Institute. The number of children with these genetic diseases is relatively small, so this sort of structure allows us to get the trials done efficiently and expediently.”

    A common underlying feature of these cancers is abnormal activity of a key signaling protein called Ras. The protein made by the NF1 gene normally restrains Ras signaling and this key “brake” is lost in tumors with NF1 mutations. In addition to playing a central role in tumors that develop in people with NF1, the NF1 gene is frequently mutated in cancers that develop in the general population such as breast and lung cancers, pediatric and adult brain tumors, melanoma and acute myeloid leukemia.

    The Ras protein is involved with more than a third of all cancers, and this research could lead to new therapies for many other cancers, Clapp said.

    “Our SPORE team applies data generated in the laboratory to guide the development of innovative clinical trials,” Shannon said. “This new NCI grant will allow us to extend this ground-breaking work that is evaluating a number of promising treatments for decreasing abnormal Ras signaling.”

    In addition to Indiana University and UCSF, collaborating institutions include the Pediatric Oncology Branch of the National Cancer Institute (NCI), Johns Hopkins University (JHU), Memorial Sloan Kettering Cancer Center (MSK), UT Southwestern Harold C. Simmons Comprehensive Cancer Center (UTSW), and Children’s Hospital of Philadelphia (CHOP) aligned in collaboration with the University of Pennsylvania Abramson Cancer Center. 

    One of 63 SPORE grants throughout the country, the IU grant remains the only one focused on childhood cancers. Additionally, while most SPORE efforts focus on a single cancer, the IU-led program—called the Developmental and Hyperactive Ras Tumor (DHART) SPORE—is working to develop new treatments for different tumors and cancers that develop due to NF1 mutations.

    “In the past five years, the group has completed a series of basic studies and clinical trials that have led to the first-ever FDA drug approval for NF1 and successful trials that are encouraging for new treatments in peripheral nerve tumors and myeloid leukemia,” Clapp said. “In this renewal, we are building on that work as well as initiating a new project focused on brain tumors that occur at higher rates in adolescents and young adults with NF1.”

    The grant includes three research projects: 

    • Project 1: Up to 50 percent of NF1 patients develop nerve tumors called plexiform neurofibromas (PNF). Researchers on this project have identified two effective drugs for treating PNF, including efforts that led to the FDA approval of selumetinib, the first drug specifically for NF1. They will build on that work to explore combination therapies and other new single drug therapies. Lead investigators on this project include Clapp; Lu Le, MD, PhD, (UTSW); Brigitte Widemann, MD, (NCI); Jaishri Blakeley, MD, (JHU); and Michael Fisher, MD, (CHOP). Luis F. Parada, PhD, (MSK) is also an investigator on this project.
    • Project 2: Young adults with NF1 are five to 10 times more likely to develop brain tumors called gliomas and glioblastoma. Additionally, the NF1 mutation can appear in gliomas even when the patient does not have the genetic syndrome. Project co-leaders Luis F. Parada, PhD, and Ingo K. Mellinghoff, MD, (both with MSK) will study the biology and possible therapies for these NF1-associated brain tumors. Jaishri Blakeley, MD, (JHU) is also an investigator on this project.
    • Project 3: Children with NF1 are also at high risk of developing juvenile myelomonocytic leukemia (JMML). Shannon and Mignon Loh, MD, (both of UCSF) are working to develop more effective and less toxic therapy for infants and children with JMML. Their findings have already led to an ongoing Phase 2 clinical trial.

    In addition, the SPORE grant includes a Development Research Program and a Career Enhancement Program, which provide funding to early-stage and established investigators to conduct research on NF1 and contribute to the overall goals of this work. 

    “The groundbreaking work done by this group in this SPORE has already been paradigm- and practice-changing and has fundamentally impacted patients in the most positive of ways,” said Kelvin Lee, MD, director of the IU Simon Comprehensive Cancer Center. “I believe the advances by Dr. Clapp and his team are only going to accelerate with this renewal.”

    Available for interview: 

    • D. Wade Clapp, MD, leader of the Specialized Programs of Research Excellence (SPORE). Clapp is chairman of the Department of Pediatrics at IU School of Medicine, the physician-in-chief at Riley Hospital for Children at Indiana University Health and a member of the IU Melvin and Bren Simon Comprehensive Cancer Center and the Herman B Wells Cancer for Pediatric Research. 
    • Mindi Hampton, a resident of southern California who brought her daughter, at the time a preschooler, to Indianapolis to take part in Clapp’s clinical trial. Hampton’s daughter Emily, now 17 and a high school senior, is alive today because of research conducted at IU. 

    Media contact: 

    Candace Gwaltney; Email: 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.

  • $2 million gift supports lung, pancreatic cancer research at IU

    $2 million gift supports lung, pancreatic cancer research at IU

    INDIANAPOLIS—In a gesture that defines gratitude and respect spanning more than 23 years, Carmel resident Ruth “Rikki” Kutcher Goldstein has made a $2 million gift to support cancer research at Indiana University School of Medicine.

    The Rikki and Leonard Goldstein Chair in Cancer Research will be held by a lung or pancreatic cancer researcher at the Indiana University Melvin and Bren Simon Comprehensive Cancer Center. The gift honors Lawrence H. Einhorn, MD, for his care of her son-in-law, S. Wyle Weiman, more than 20 years ago. Though Wyle unfortunately died of lung cancer, the family remains grateful for the expertise and compassion that Einhorn provided. Since 1998, the Goldsteins have provided annual support to Einhorn’s research.

    “All Hoosiers should be grateful for the impact Larry has had on cancer research during his career at IU,” Rikki Goldstein said. “Our family is thrilled to honor him by ensuring that IU can continue to recruit and retain top-notch researchers like him.” 

    Einhorn, who is internationally known for his role in developing the chemotherapeutic cure for testis cancer in the 1970s, has been a faculty member at IU School of Medicine since 1973. Over his career, he has mentored and trained more than 100 oncologists and provided care to countless patients. His work continues to focus on testis and lung cancers. 

    The Goldsteins have a long history of generous support of Indiana University. Rikki Goldstein and her late husband Leonard (Len) generously supported the IU Borns Jewish Studies Program and established the Leonard M. and Ruth K. Goldstein Matching the Promise Scholarship in Jewish Studies.

    “In our family, we believe that giving and volunteering are important traditions," she said. “My parents taught me to support those in need. As a matter of fact, it's almost a requirement in Judaism. The word is ‘tzedakah,’ and it means responsibility. Being able to do this is really exciting for me and for all our kids, too.” 

    The Goldsteins, who were married for 71 years before Len’s death at the age of 97 in 2018, are the parents of four adult children: Michael, Steven and Jan Goldstein and Lisa Post. They also have eight grandchildren and four great-grandchildren. 

    After being an active volunteer at her children’s schools, Rikki Goldstein re-entered the workforce and, while working, earned her bachelor’s degree at age 50 from Indiana University Purdue University Fort Wayne (now Purdue University Fort Wayne). In 1976, she was a founding mother of the Fort Wayne Women’s Bureau, where she worked as director of peer counseling supervising programs that helped women re-enter the workforce after a divorce or death of a spouse.

    In 1996, at age 70, Rikki Goldstein began working for the Neighborhood Health Clinics in Fort Wayne. For 20 years, she served as a medical social worker and directed outreach programs before retiring in August 2016.

    “Medical research is very meaningful to me professionally as well as personally,” she explained. “That’s one of the reasons I am particularly delighted to make this gift.”

    Rikki Goldstein helped found the Fort Wayne Ballet and served on its board of directors. The Goldsteins both served on the board of directors of the Planned Parenthood organization during its early years in Fort Wayne.

    In 1994, Rikki and Len Goldstein were each appointed Sagamores of the Wabash by then-Governor Evan Bayh. One of the highest honors an Indiana governor can give, the award is presented for distinguished service to the state or governor.

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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 launches new study to develop personalized therapies for triple-negative breast cancer patients

    IU School of Medicine launches new study to develop personalized therapies for triple-negative breast cancer patients

    Stratification of at-risk patients made possible by building on foundation of previous discovery made by IU research team 

    INDIANAPOLIS – Indiana University School of Medicine researcher Bryan P. Schneider, MD, is leading a novel nationwide study to better understand how to treat patients with triple-negative breast cancer based on their own unique genetic data. 

    PERSEVERE is a phase 2 clinical trial with the goal of studying personalized cancer treatment combinations when compared to standard cancer treatment. 

    “There is a tremendous need for successful triple-negative breast cancer treatments,” said Schneider, who is the Vera Bradley Professor of Oncology at IU School of Medicine and a physician-scientist at the IU Melvin and Bren Simon Comprehensive Cancer Center and the Vera Bradley Foundation Center for Breast Cancer Research. “Recurrence and death rates are still too high, and novel strategies to improve that are markedly needed. We feel PERSEVERE is an innovative trial to try to help meet those needs.”

    While approximately one-third of patients with triple-negative breast cancer will achieve remission after surgery and chemotherapy, two-thirds will have some cancerous tissue in their body. Recent research shows that patients who test positive for circulating tumor DNA (ctDNA) – tumor cell pieces found in the blood stream – after surgery are at higher risk of their cancer returning. PERSEVERE will enroll 200 participants and test whether there is ctDNA in their blood. 

    If a participant tests positive for ctDNA, the researchers will look at the DNA of their blood and tumor to see if there are any genetic differences that can be treated with a genomically targeted therapy or a standard treatment. There are several possible combination therapies that these participants may receive based on their genetic differences. 

    If a participant tests positive for ctDNA but researchers determine they do not have a specific genomic target in their blood or cancer tissue, they will receive a standard treatment recommended by their doctor. Participants who test negative for ctDNA may receive a standard treatment, but they will also have the option to receive no treatment and remain in the study for observation. 

    “Based on the data that came out of our group, we have shown that circulating tumor DNA is also a very powerful risk stratifier,” said Schneider. “In this trial, we’ll capitalize on that powerful ability to better focus our attention on novel therapies for those patients at extraordinarily high risk who have ctDNA positivity. Equally importantly, it will provide the opportunity for us to focus on those who do not test positive for ctDNA, a group that may be expected to do quite well in terms of deescalating therapy and improving quality of life.” 

    PERSEVERE builds on a previous discovery by Schneider and colleagues in which they found that the presence of ctDNA and circulating tumor cells (CTCs) in the plasma of women’s blood who have undergone chemotherapy before surgery for triple-negative breast cancer treatment are critical indicators for the prediction of disease recurrence and disease-free survival. 

    Their findings from the BRE12-158 study were first presented at the 2019 San Antonio Breast Cancer Symposium, the most influential gathering of breast cancer researchers and physicians in the world, and then published in the prestigious medical journal JAMA Oncology

    Researchers will follow up with all participants for up to five years to check for side effects, as well as signs of cancer recurrence. This study hopes to determine better treatments for those fighting triple-negative breast cancer by looking at characteristics that are unique to each participant’s cancer. 

    The PERSEVERE study is funded by the Indiana University Precision Health Initiative Grand Challenge, the Vera Bradley Foundation for Breast Cancer, Genentech Roche, Pfizer, Foundation Medicine and Epic Sciences. The study is being managed by the Hoosier Cancer Research Network and will enroll at 20 clinical sites across the United States. 

    Media Contacts: 

    Anna Carrera | acarrer@iu.edu, 614-570-6503 (cell)
    Christine Drury | cldrury@iu.edu, 317-385-9227 (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 and 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 discover small molecule degrader as potential anticancer drug

    Unique approach unlocks opportunity for previously undruggable cancerous targets to be discovered

    INDIANAPOLIS—Researchers in the Department of Pathology and Laboratory Medicine at Indiana University School of Medicine have discovered a novel anti-cancer drug, using a unique approach that has allowed them to target previously undruggable cancerous proteins. When traditional drug discovery approaches failed, Anita Bellail, PhD, Chunhai Charlie Hao, MD, PhD, and their team developed a cancer cell-based screening to identify a lead compound known as HB007, which slowed cancer growth in models. Their findings were published this month in Science Translational Medicine. 

    “All proteins go through a life cycle from gene transcription to protein degradation,” said Bellail, the lead author who is an assistant professor of pathology and laboratory medicine at IU School of Medicine. “The cancerous proteins are highly expressed in part due to the blockage of degradation. Targeted protein degraders such as HB007 can release the blockage and send the proteins to the trash can.”

    In the past, researchers have searched for compounds known as inhibitors to directly bind to and inhibit cancerous proteins, but the vast majority of proteins lack binding pockets. The next generation of drugs that Bellail, Hao and team are working to identify are small molecule degraders that target the protein degradation pathway for the destruction of cancerous proteins and shutdown of cancer growth. 

    Eighty percent of proteins in the human body are currently undruggable. The team led by Bellail and Hao, who are members of the IU Melvin and Bren Simon Comprehensive Cancer Center,  designed and utilized a cancer cell-based drug screening process to identify the first small-molecule degraders of a cancerous protein called SUMO1, which was previously considered undruggable. The team has also discovered the novel CAPRIN1-CUL1 ubiquitin ligase that compound binds to and leads to SUMO1 recruitment to the ligase for destruction.  

    “We believe we are the first ones to report the step-by-step process of how to find the small molecule degraders of undruggable proteins,” said Hao, a senior author who is the Bicentennial Professor of Pathology and Laboratory Medicine and Neurological Surgery at IU School of Medicine and a member of the Vera Bradley Foundation Center for Breast Cancer Research at the cancer center. “This will generate a strategy that can help researchers find small molecule degraders as novel drugs. Since the degraders can destroy the proteins, the dose can be much lower, so efficacy is also much better.”

    Bellail, Hao and colleagues tested their theory by observing patient-derived brain, breast, colon and lung cancers in animal models. Their approach suppressed the cancers and increased the survival of the animals. This approach may be useful for identifying other small-molecule degraders of cancerous proteins as the next generation of anticancer drugs. 

    Bellail and Hao came to IU School of Medicine in 2018 with the goal of building up novel drug discovery programs. 

    This work was supported in part by the Pathology Bicentennial Chair endowment and start-up fund, the Indiana University School of Medicine Physician Scientist Initiative funded by Lilly Endowment Inc., IU Simon Comprehensive Cancer Center’s 100 Voices of Hope program, the Vera Bradley Foundation for Breast Cancer Scholar fund, and National Institutes of Health grants R01CA203893 and R43CA224461.   

    Media contact
    Anna Carrera | Email: acarrer@iu.edu | Cellphone: 614-570-6503

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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 Simon Comprehensive Cancer Center names its first associate director of diversity, equity and inclusion

    IU Simon Comprehensive Cancer Center names its first associate director of diversity, equity and inclusion

    INDIANAPOLIS — The Indiana University Melvin and Bren Simon Comprehensive Cancer Center has named Antwione Haywood, PhD, its associate director of diversity, equity and inclusion (DEI). Haywood is the first person to hold the chief diversity officer position at the cancer center. 
     
    Haywood, assistant dean for medical student affairs and assistant professor of clinical radiation oncology at Indiana University School of Medicine, joins the cancer center’s executive committee, which oversees strategic planning, major funding decisions, and clinical, research, and educational activities. 

    Equity and inclusion have been a common thread throughout Haywood’s career. His work has included projects investigating disparities in access, retention, and support of underrepresented populations. His DEI efforts have led to multiple publications and oral and poster presentations at national meetings.

    Haywood serves as a co-director for the Cancer in the Under-Privileged Indigent or Disadvantaged (CUPID) summer fellowship, a program within the cancer center and the medical school. The CUPID program cultivates an interest in oncology and cancer research among medical students and includes formal lectures discussing health care disparities and specific diseases prevalent in underserved populations. Haywood teaches the Mind Body Medicine elective course for IU medical students, which promotes mindfulness and wellness practices. Within IU School of Medicine, he conducts unconscious bias training for faculty and students, leading tough conversations around DEI issues.

    “Dr. Haywood brings great knowledge, passion and experience to our efforts to build diversity, equity and inclusion into the moral foundation of the IU Simon Comprehensive Cancer Center,” Kelvin Lee, MD, director of the IU Simon Comprehensive Cancer Center, said. “We are very fortunate and very excited to have him join our team.”
    Haywood joins the cancer center at an integral time as the National Cancer Institute (NCI) has charged all NCI-designated centers to increase DEI efforts. He will be responsible for enhancing participation of women and underrepresented populations in the research workforce and center leadership; supporting career-enhancing research opportunities for junior, early- and mid-career researchers to prepare them for center leadership; expanding the pipeline of cancer center members of diverse backgrounds through training or mentoring opportunities; and leveraging institutional commitment to enhance diversity within the center’s membership and leadership.

    Haywood previously was director of the Academic Success Center at Purdue University. While there, he helped launch a national tutor training program and oversaw various initiatives to improve success of historically underrepresented populations in higher education.

    Haywood holds a PhD from Indiana University-Bloomington, a master’s degree from the University of Kansas, both in higher education, and a bachelor’s degree in marketing from Old Dominion University.

    “This is such a pivotal time to be joining the IU Simon Comprehensive Cancer Center team,” Haywood said. “It’s really important to support creating spaces that values equity and inclusivity. An equity-centered approach to our work will advance our strategic focus on becoming a socially responsible comprehensive cancer center.”
  • Cancer center researchers part of a collaborative $12.4 million SPORE grant from National Cancer Institute

    Cancer center researchers part of a collaborative $12.4 million SPORE grant from National Cancer Institute

    IU research could lead to new treatment options for breast and ovarian cancer patients

    INDIANAPOLIS—Two Indiana University Melvin and Bren Simon Comprehensive Cancer Center researchers are now part of a prestigious Specialized Programs of Research Excellence (SPORE) grant from the National Cancer Institute.

    Kathy Miller, MD and Ken Nephew, PhD are among nearly 20 scientists at six institutions who will work to improve epigenetic therapies for cancer with the five-year, estimated $12.4 million grant.

    The SPORE grant was awarded to The Coriell Institute for Medical Research (Camden, NJ) and Van Andel Institute (Grand Rapids, MI) and includes three research projects focusing on epigenetic therapy, which aims to treat cancer by correcting abnormal gene expression.

    The project at Indiana University will investigate the impact of epigenetic therapy on cancers driven by BRCAness, a major cancer-related vulnerability. Nephew and Miller, both researchers at the Vera Bradley Foundation Center for Breast Cancer Research at the IU Simon Comprehensive Cancer Center, will collaborate with project co-investigator Feyruz Rassool, PhD, of the University of Maryland School of Medicine.

    Patients who inherit mutations in the BRCA1 or BRCA2 genes are at higher risk for breast and ovarian cancers. While approved therapies exist for those patient populations, those therapies won’t work for women diagnosed with triple negative breast cancer or ovarian cancer with BRCAness—a defect in the DNA repair process that imitates BRCA mutations, even though the gene is intact. This research could offer a treatment approach for both BRCA mutant and intact cancers.

    “We are pioneering an epigenetic therapy-PARP inhibitor combination that will generate a vulnerability in cancer cells. Our strategy represents a potentially important treatment advance and therapeutic option for women diagnosed with breast or ovarian cancer who lack BRCA mutations and address an urgent clinical need,” Nephew said.

    Nephew is assistant director of research-Bloomington and co-leader of the Tumor Microenvironment and Metastasis research program at the cancer center and Jerry W. and Peggy S. Throgmartin Professor of Oncology at IU School of Medicine. Nephew traces his work testing the combination of epigenetic therapy and PARP inhibitors in mouse models with breast cancer metastasis to generous funding from 100 Voices of Hope.

    “We are also pre-clinically testing whether the efficacy of this treatment strategy may be further enhanced by including immune checkpoint therapy,” Nephew said. “Cancer immunotherapy has yet to achieve meaningful survival benefit in breast and ovarian cancer patients. Epigenetic drug approaches for epigenetic immunosensitization could be a game-changer.”

    Miller, Nephew and collaborators will explore possible benefits of epigenetic combination therapies for patients with triple negative breast cancer and ovarian cancer patients who are resistant to PARP inhibitor (PARPi) therapy. PARP is an enzyme in cells that help repair damaged DNA; the PARP inhibitors work by blocking cancer cells from repairing the damage. The research could bring the benefits of PARPi therapy to a larger group of patients, offering more treatment options.

    “We began the first clinical trial combining epigenetic therapy with a PARP inhibitor last year, exploring different doses and learning how to use the combination safely. With support from the SPORE grant, we can expand that initial trial and study how this combination controls breast and ovarian cancers,” Miller said. Miller is associate director of clinical research at the cancer center and the Ballvé-Lantero Professor of Oncology at IU School of Medicine.

    “Blood and tumor samples collected from patients in the trial will complement the work Dr. Nephew and Dr. Rassool are doing in the lab, helping us to better understand how the combination works and which patients are most likely to benefit,” Miller said.

    Researchers on this SPORE grant have collaborated on epigenetic research for many years. In 2018, Miller and Nephew were named to the Van Andel Institute–Stand Up To Cancer (SU2C) Epigenetics Dream Team, a multi-institutional effort to identify new and more effective cancer therapies and test them in the clinic to improve patient care. The VAI-SU2C Epigenetics Dream Team has launched more than a dozen epigenetic therapy clinical trials in recent years and will support trials from this SPORE.

    “SPORE grants are the highest level of research funding dedicated to moving science from the laboratory to cancer patients, and they have great impact in advancing new and innovative approaches in cancer care and treatment,” said Kelvin Lee, MD, director of the IU Simon Comprehensive Cancer Center. “The very impressive research project of Drs. Nephew, Rassool and Miller is at the heart of clinical research in this epigenetics SPORE; it has the real potential to be a groundbreaking approach for some of the hardest to treat breast and ovarian cancers.”

    This SPORE grant is the first in NCI history to support a thematic focus on epigenetics and can be renewed indefinitely. Read more about the grant and additional projects on the NCI website.

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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.

  • 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.