• 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.

  • IU School of Medicine researchers publish first scientific article dedicated to Tyler Trent’s donated tumors, his legacy

    IU School of Medicine researchers publish first scientific article dedicated to Tyler Trent’s donated tumors, his legacy

    INDIANAPOLIS—Researchers at Indiana University School of Medicine have published their work about a specific type of childhood cancer in the peer-reviewed, international oncology journal, Cancers. This research involves a combination therapy that significantly slows tumor growth in models, which includes a model established from cells taken from tumors donated by Tyler Trent. This is the first published manuscript that includes Trent’s tumor model. 

    Trent was a Purdue University student and sports superfan who died on January 1, 2019, after waging a long and valiant fight against an aggressive form of bone cancer known as osteosarcoma. In the publication’s acknowledgments, the researchers dedicated the study to Trent’s memory, saying they will always remember him for his courageous battle, his passion for cancer advocacy, and the generous donation of his tumor tissue for research.

    “We are so proud to honor Tyler’s legacy with this first publication, laying the foundation for future research to build upon,” said Karen E. Pollok, PhD, who led the study. Pollok is an associate professor of pediatrics at IU School of Medicine. “We still have more work to do, but are hopeful that new therapies for osteosarcoma will be possible as we learn more about how to block different tumors from growing.” 

    The Precision Genomics team at Riley Children’s Health found a genetic variation in Trent’s tumors (named after him as TT1 and TT2) known as the MYC-RAD21 signature, which has been found in tumors that tend to recur. Pollok said there are two drugs that can block its effects, a Chk1 inhibitor and a bromodomain inhibitor. Her team tested each drug individually, as well as in combination. They found that in models with the TT2 tumor, they could stop the tumors from growing by using one of the drugs individually, but using both drugs together blocked tumor growth substantially during a four-week treatment. The research team also determined that the combination treatment was well-tolerated. 

    “This research is allowing us to forge a path to improving outcomes for children, adolescents and young adults with a very aggressive bone cancer,” said Jamie Renbarger, MD, another one of the lead researchers. Renbarger was one of Tyler’s doctors and also leads the IU Precision Health Initiative pediatric sarcoma disease research team. She is also the Caroline Symmes Professor of Pediatric Cancer Research at IU School of Medicine. “We are hopeful that this program will lead the way in finding cures for more children.”

    The tumor started growing in the models again after stopping the therapy, leading researchers to consider next steps in their scientific process. Future research topics will include learning to understand how the tumors adapt to treatments and finding ways to optimize the combination therapy. 

    “The findings and research going on with Tyler’s tumor models is incredibly encouraging and comforting to Tony and I,” said Kelly Trent, who is Tyler Trent’s mother. “It was at the core of who Tyler was to want to be used for good and to help at this capacity. We are so grateful for Dr. Pollok and Dr. Renbarger’s work.”

    Trent was diagnosed with osteosarcoma for the first time when he was 15 years old. In the years that followed while he was a patient at Riley Hospital for Children at IU Health, he donated several tumor samples to cancer researchers at IU School of Medicine. He also encouraged other people to do the same, becoming a national advocate for cancer research. People have donated millions of dollars for cancer research in his name, including more than $189,000 for the Tyler Trent Cancer Research Endowment for Riley Hospital. The Trent family and Riley Children’s Foundation worked together to create the endowment fund, which supports pediatric research being conducted by IU School of Medicine researchers. 

    Kelly and Tony Trent have also recently started working with Grainne Owen, one of the co-founders of Curing Kids Cancer. The non-profit organization supports research for childhood cancer. This past year, Pollok and her colleagues competed for and received a $150,000 grant from Curing Kids Cancer to support research with Tyler’s models. 

    This research is being conducted at the Herman B Wells Center for Pediatric Research at IU School of Medicine. Both Pollok and Renbarger are researchers at the IU Simon Comprehensive Cancer Center

    Funding for this research was also provided by the Indiana University Grand Challenge Precision Health Initiative (with one of its focuses being on finding a cure for pediatric sarcomas, including osteosarcoma), the NIH/NCI Cancer Center Support Grant P30CA082709 awarded to the Indiana University Simon Comprehensive Cancer Center, and the Tyler Trent Cancer Research Endowment for Riley Hospital for Children at IU Health. 

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

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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.

  • Cancer center researcher receives $1.3 million grant to improve breast cancer treatment for Black women

    Cancer center researcher receives $1.3 million grant to improve breast cancer treatment for Black women

    INDIANAPOLIS -- An Indiana University Melvin and Bren Simon Comprehensive Cancer Center researcher is identifying the unique biology that may make Black women more susceptible to aggressive breast cancer.

    Harikrishna Nakshatri, PhD, received a $1.3 million grant from the Department of Defense – Congressionally Directed Medical Research Program’s breast cancer research program. Nakshatri is associate director of education at the cancer center and the Marian J. Morrison Professor of Breast Cancer Research at Indiana University School of Medicine

    The grant will allow Nakshatri to continue to characterize unique biomarkers within the normal breasts of Black women and how that impacts health disparities in breast cancer.

    The research could lead to improved treatments for Black women, who face a higher mortality rate for breast cancer.

    “The vast majority of people think of health disparities from the point of view of socio-economic factors, but we are looking at the biologic factors or the biologic basis of health disparities,” Nakshatri said. “This doesn’t account for all cases of health disparity, but there is a certain section where it may inform treatment.”

    Nakshatri’s research has shown that normal breast tissue in Black women contains a cell type called PZP at a much higher number when compared to normal breast tissue of Caucasian women. PZP cells increase in number when Caucasian women develop breast cancer, while they are naturally higher in Black women. Nakshatri’s lab is exploring the nature of these PZP cells, if breast cancer can originate from these cells and their role in helping cancer grow. 

    While Black women develop cancer at the same rate as women of other racial and ethnic backgrounds, the cancer often occurs at a younger age and is more aggressive. Another biologic explanation may come from a genetic mutation called duffy, which is present in Black women with sub-Saharan Africa ancestry.

    “That mutation is embedded in this population because it protects them against malarial infection,” said Nakshatri, who is also a researcher at the Vera Bradley Foundation Center for Breast Cancer Research. “Current research has shown that when women who carry this mutation develop breast cancer, it tends to be much more aggressive.”

    Nakshatri analyzed DNA from 100 Black women and found that about 40 percent carried this mutation. He then used normal breast tissue of duffy mutation carriers and compared it to cells from African American women who do not carry the mutation. The tissue samples were from the Susan G. Komen Tissue Bank at the IU Simon Cancer, the world’s only collection of healthy breast tissue

    “What we found was that the normal breast cells of these duffy carrier women already have signaling molecules for cancer initiation at a much higher level,” he said. “That gives me an explanation of why they may develop breast cancers that are aggressive.” 

    Already there are existing cancer drugs that target these signaling molecules, but they have not been tested for targeted therapy for specific genetic cases. Nakshatri will use an animal model to find out if those drugs can be used to target breast cancer in Black women who carry the duffy mutation. 

    “The question we are asking is: Do these women need a different type of treatment if they are carriers of this mutation? Should they go through conventional treatment, or can we add or subtract some of the treatments to make them respond better?” Nakshatri said. “There are many drugs out there that we still need to figure out who will benefit from them; that is our ultimate goal.” Although this research is in the preclinical stage, Nakshatri hopes these findings will lead to clinical studies in the coming years.

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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 researcher receives $2.9 million for work improving effectiveness in lung cancer radiation therapy

    IU researcher receives $2.9 million for work improving effectiveness in lung cancer radiation therapy

    INDIANAPOLIS -- An Indiana University Melvin and Bren Simon Comprehensive Cancer Center researcher has been awarded a five-year, $2.9 million grant from the National Cancer Institute to develop a drug that could make radiation therapy far more effective.

    John Turchi, PhD, is studying the DNA-dependent protein kinase (DNA-PK), which is involved in repairing DNA double-strand breaks. When a cancer patient undergoes radiation therapy, the radiation intentionally causes these DNA breaks to kill the cancer cells.

    “In the case of radiation therapy, the repair of those breaks is a bad thing,” Turchi said. “It allows the cancer cells to continue to divide. Being able to block that repair pathway through inhibitors of the DNA-PK protein allows us to increase the efficacy of radiation therapy.”

    The research focuses on solid tumors that receive radiation therapy as part of treatment, with lung cancer as the main effort. The therapeutic would be given along with radiation. 

    “In addition to lung cancer, esophageal and head and neck cancers could also benefit. Radiation therapy is a mainstay for these cancers and, we think we can increase the therapeutic benefit of radiation with our drug,” said Turchi, the Tom and Julie Wood Family Foundation Professor of Lung Cancer Research at Indiana University School of Medicine.  

    Beyond occurring due to radiation therapy, DNA double-strand breaks also can happen in cancer cells as they continuously divide and grow. The therapeutic could be used for certain cancers that don’t receive radiation therapy by targeting these broken cells.

    “The grant focuses on understanding how cells respond to stress—specifically DNA damage stress—and exploiting the differences between how cancer cells respond and how normal cells respond for therapeutic benefits,” Turchi explained. “Essentially, we are pursuing a line of research to develop drugs that exploit the differences in how cells respond to DNA damage stress.”

    This research could expand the DNA-PK inhibitor options for cancer patients. While there are investigational drugs in the clinic, Turchi’s therapeutic uses a different mechanism of action and could expand options for patients who don’t respond to the existing drugs or whose cancer has become resistant to therapy.

    “Our molecule does something completely different,” Turchi said. “There are reasons to believe that our inhibitor allows a greater scope of possibilities for cancers than what is currently being tested in the clinic. Because of this different mechanism of action, it opens up a whole array of things that aren’t possible with the existing therapeutics.”

    Turchi and colleagues also are exploring how their molecule could target ovarian cancer with certain genetic predispositions, such as the BRCA mutation. In these cases, the cancer is more susceptible to the drug and could be effective without radiation.

  • Walther Cancer Foundation $11 million investment to expand IU-Purdue bioinformatics collaboration

    Walther Cancer Foundation $11 million investment to expand IU-Purdue bioinformatics collaboration

    The Walther Cancer Foundation will invest $11 million to advance collaborative cancer research at Indiana University and Purdue University by supporting scientists through bioinformatics—an increasingly critical aspect of their work. 

    Bioinformatics involves managing and analyzing the massive amounts of data generated by scientific research—turning data into knowledge that could lead to new cancer treatments.

    “We hope this gift enables scientists at IU and Purdue to dig more deeply and refine their studies so they can point out new pathways to good patient outcomes in cancer,” said Tom Grein, president and CEO of the Walther Cancer Foundation. “Sometimes, you have so much data, it’s hard to comprehend where it’s leading you. I hope the data-driven analysis will uncover nuggets of opportunity that would otherwise never be seen.” 

    Income from the new Walther Cancer Foundation Bioinformatics Fund will continuously support bioinformatics personnel, technology, and other tools shared by the cancer research programs at both universities. In addition, IU and Purdue will make their own investments into the fund. 

    “The Walther Cancer Foundation leadership understands the central importance of data and analytics in developing better treatments and, ultimately, cures for cancer,” said IU School of Medicine Dean Jay L. Hess, MD, PhD, MHSA. “We are tremendously grateful for their support and the confidence they have in our work.”

    Timothy Ratliff, the Robert Wallace Miller Director of the Purdue Center for Cancer Research, said the latest gift from the Walther Foundation is a continuation of a longstanding collaboration, commitment and investment that will build on the center’s success in cancer drug discovery and development—and will help sustain the center’s Computational Genomics and Bioinformatics Core for years to come. "Once again, we are grateful to the Walther Cancer Foundation’s vision and generosity, which is so important to our research and success. This continuing partnership—plus our own investments and fundraising—will secure what we’ve already established, and enable us to grow into the future."

    Kelvin Lee, MD, named this week as the new director of the IU Melvin and Bren Simon Comprehensive Cancer Center, said having strong capabilities in bioinformatics is essential to cancer research.  

    “The genetic, biochemical, cellular and immune pathways that can lead to cancer are extraordinarily complex and intertwined. Recent cutting-edge advances in technology means that researchers now have unprecedented amounts of data on these pathways, but this seriously challenges our ability to analyze these huge mounds of information to make sense of what is actually going on,” Lee said. “We are fortunate that the Walther Cancer Foundation understands that breakthroughs require the expertise and the tools, like artificial intelligence (AI), to help us analyze all this data so we can understand what’s really important.” 
      
    This level of collaboration—and sharing of a key resource like a bioinformatics core—is unusual among a pair of National Cancer Institute-designated cancer centers. But it also reflects the complementary nature of the two institutions.

    Purdue’s Center for Cancer Research is a basic science cancer research center with more than 110 researchers that is a leader in biomedical engineering and cancer drug development.

    The IU Simon Comprehensive Cancer Center is a comprehensive cancer center with nearly 250 cancer researchers who conduct basic lab work and drug development but who are also engaged in clinical care and population health research.

    “Each of them has different capabilities, different levels of expertise, different interests,” Grein said. “But when you get scientists to collaborate, the outcomes are better.”

    Since its founding in 1985, the Walther Cancer Foundation has invested more than $165 million in cancer-focused medical research, and in research and education aimed at supporting cancer patients and their families.

    Walther has previously supported cancer bioinformatics at IU and Purdue on a year-to-year basis. This new gift establishes a fund that will ensure the bioinformatics work continues in perpetuity.

    The Walther Foundation endowment provides the opportunity to develop the expertise and the tools that are needed to face current and future challenges in biology and the cancer field, said Majid Kazemian, an assistant professor in Purdue’s departments of biochemistry and computer science. His research focuses on integrating computational and experimental approaches to study pathogen interaction with host cells and immune system in infectious diseases and cancers caused by pathogens. 

     "The Purdue University Center for Cancer Research has nearly 100 investigators who are actively engaged in understanding molecular mechanisms of various diseases including lung, liver and prostate cancers, many of which have begun to utilize genomics data in their studies,” Kazemian said. "Large genomic public data on many diseases generated over the last decade are a treasure trove of unexplored information. Walther Foundation's funds endowment will enable analysis of big data generated by our center’s members and collaborators as well as an exploration of growing public genomics data to contextualize and translate our findings."  

    Less-costly access to bioinformatics expertise and resources enabled by Walther Foundation will open up new avenues for many of the Purdue center's scientists to broaden the impact and clinical translation of their discoveries, Kazemian said. "It will also encourage our scientists to perform large-scale genomics assays and will foster new collaborations.” 

    IU School of Medicine breast cancer researcher Harikrishna Nakshatri, PhD, said he relies on bioinformaticians to design experiments, analyze data and assist him in publishing research results more quickly. The Walther Foundation gift supports that very expensive process, and the collaboration means researchers have more bioinformaticians available when they are needed. All of it combines, Nakshatri said, to enable scientists to reach conclusions that have real benefits for patients.

    “If you really believe in your hypothesis,” Nakshatri said, “now you have a chance to test it because you are not burdened by the financial aspects.” 

    According to Hess, the new resources will allow IU’s partnership with Purdue to continue to improve the health of Hoosiers. “We have worked closely for decades,” Hess said. “This new collaboration in data sciences will accelerate our ability to benefit cancer patients across the state—and far beyond.”

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

    About the Walther Cancer Foundation
    The Indianapolis-based Walther Cancer Foundation is a private grant-making foundation that supports and promotes interdisciplinary and inter-institutional cancer research, both bench and clinical. The clinical research it supports encompasses clinical trials as well as behavioral studies, the latter as part of the foundation’s commitment to Supportive Oncology. The Walther Foundation has two primary goals: to support cancer research with the aim of discovering better treatments, if not cures, and to develop a comprehensive approach for supporting patients with cancer and their families. Since its founding, the foundation has invested over $165 million cancer-focused research.

    About the Purdue Cancer Center
    Since 1978, the Purdue University Center for Cancer Research has been a National Cancer Institute-designated basic-research cancer center. Only seven institutions in the United States have earned this title. Being a basic-research center means it does not treat cancer patients directly. Its work focuses on investigating cancers where they begin—at the cellular level—to investigate the cause of, and cure for, one of the most devastating killers of our time. Doctors and scientists throughout the world use the center’s discoveries to develop methods, medicines and medical devices to save and enhance patient lives. 


  • IU School of Medicine names new cancer center director, announces $15 million supporting gift from Walther Cancer Foundation

    IU School of Medicine names new cancer center director, announces $15 million supporting gift from Walther Cancer Foundation

    INDIANAPOLIS—Indiana University School of Medicine has announced the hiring of a world-recognized medical oncologist and multiple myeloma researcher to lead the Indiana University Melvin and Bren Simon Comprehensive Cancer Center, bolstered by a $15 million fund established by the Walther Cancer Foundation to support him in this role.   

    Kelvin Lee, MD, has been named the new IU Simon Comprehensive Cancer Center director. In addition, Lee will hold the titles of senior associate dean of cancer research at IU School of Medicine and the H.H. Gregg Professor of Oncology. He will also direct the Cancer Institute, an umbrella entity designed to facilitate collaboration among cancer disciplines at IU School of Medicine and Indiana University Health, enhancing clinical research opportunities for patients here in Indiana and beyond. He will have appointments with both the Department of Medicine and the Department of Microbiology and Immunology.  

    Since 2006, Lee has served as the Jacobs Family Chair of Immunology at the Roswell Park Comprehensive Cancer Center in Buffalo, New York. The co-leader of the Cancer Center Tumor Immunology and Immunotherapy Program from 2006 to 2018, Lee led the group through three successful National Cancer Institute Cancer Center Support Grant renewals before stepping down to take on the position of Senior Vice President for the Basic Sciences.

    The IU Simon Comprehensive Cancer Center has long been a leader in the field. It was recognized in 2019 as one of the top cancer research institutions in the nation when it was designated a Comprehensive Cancer Center by the National Cancer Institute. Home to the cure of testicular cancer, the IU Simon Comprehensive Cancer Center is a critical piece to IU School of Medicine’s world-class research enterprise. The central hub for cancer research across Indiana University, the center’s nearly 250 researchers 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.

    “Dr. Lee is the ideal leader to build on the IU Simon Comprehensive Cancer Center’s tremendous momentum. The center’s researchers are making great strides in improving health in current and future patients alike through their world-class care and groundbreaking research,” said Jay L. Hess, MD, PhD, MHSA, dean of IU School of Medicine and IU’s executive vice president for clinical affairs. “As an institutional leader, Dr. Lee will play a pivotal role in advancing these goals, and I’m excited for him to join our team at IU School of Medicine.” 

    As cancer center director, Lee will also play a key role in setting the future course for two significant centers at IU School of Medicine—the Vera Bradley Foundation Center for Breast Cancer Research and the Brown Center for Immunotherapy. The recruitment of a top-notch physician-scientist like Lee broadens the range of possibilities for the groundbreaking and potentially synergistic research taking place at both centers. 

    “We are very pleased to welcome one of the country’s top cancer physician-researchers to IU Health,” said Dennis M. Murphy, president and chief executive officer, Indiana University Health. “He joins an already respected program and will play a critical role in advancing our efforts, through the IU Simon Comprehensive Cancer Center and our new Cancer Institute, to expand access to cutting-edge cancer care to patients across and beyond Indiana.”

    Lee assumes leadership at a time when the IU Simon Comprehensive Cancer Center will play a large role in a continued push by IU School of Medicine and IU Health leadership to improve alignment across education, research and clinical care. Earlier this year, the establishment of three institutes was announced, covering the key research areas of cardiovascular, neuroscience and cancer. Transcending multiple departments and centers, the goal of these institutes is to fully realize the promise of academic medicine and better address the most pressing challenges facing patients.

    “I am very excited to join IU School of Medicine to continue to build the world-class effort in cancer research, education and care for the people of Indiana, nationally and globally. The renewal of the IU Simon Comprehensive Cancer Center core grant and achievement of comprehensive designation speaks to the outstanding faculty and staff that are leading this charge,” said Lee. “I have also been incredibly impressed by the deep commitment of IU School of Medicine and IU Health in these efforts, and this was a major reason in my decision to join IU.

    “I believe that research cures cancer. For this to be successful, we need to get our science into our patients. The Cancer Institute and IU Simon Comprehensive Cancer Center are well-poised to grow this effort exponentially and will light the way to ending cancer’s darkness.”

    As a physician-scientist, Lee’s research interests are both laboratory and clinical based. In the lab, his research efforts are RO1-funded and primarily focus on multiple myeloma, as well as myeloid dendritic cell differentiation in cancer. Lee currently sees patients with multiple myeloma once a week in clinic and is the principal investigator on active clinical trials of immunotherapy in myeloma at Roswell Park. 

    Lee officially assumes his new role in February 1, 2021. He succeeds Patrick J. Loehrer, MD, who served as cancer center director since 2009. Loehrer led the center through two National Cancer Institute competing renewals, which culminated with the center earning the prestigious Comprehensive Cancer Center designation. He will continue to see patients with gastrointestinal and thymic malignancies and carry on his work focused on global oncology and health equities.

    Walther Cancer Foundation announces major gift
    To help support the Cancer Institute, the Walther Cancer Foundation will contribute $15 million to establish a fund for investments in areas of cancer research and laboratory improvements that the director deems most promising.

    The Walther Cancer Foundation IU Simon Comprehensive Cancer Center Director’s Fund is intended to provide the resources and flexibility needed to advance the work of a world-class cancer center, said Tom Grein, President and CEO of the Walther Cancer Foundation.

    “It is not Walther’s position to decide, ‘This is where we want you to invest or that you need to use these funds in this explicit manner,’” Grein said. “It’s really more to give the director, who is recognized as a leader in cancer research, the ability to make those choices.”

    The Walther Cancer Foundation will continue to fulfill previous commitments to IU cancer research through 2025, at which point its gifts to the Director’s Fund are scheduled to begin and continue for three years. 

    “This incredible gift from the Walther Cancer Foundation will be a tremendous asset in the years to come, offering the flexibility to add resources and attract talent to areas where there is a need,” Lee said.

    Grein said the Walther Cancer Foundation was delighted by the cancer center’s comprehensive designation last year. And leaders at IU said it’s clear that the foundation’s support was a key ingredient in that success. 

    “The Walther Cancer Foundation’s generous support has been an essential element in the progress we’ve made in cancer research and in efforts to support the families of cancer patients,” Hess said. “We’re grateful for the confidence Walther has shown in us as we confront cancer in the lab, in the clinic and in our communities.”

    Media contact: Katie Duffey, kaduffey@iu.edu, 765-427-3553 (cellphone)

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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 Walther Cancer Foundation
    Since its founding in 1985, the Walther Cancer Foundation has invested more than $165 million in cancer-focused medical research, and in research and education aimed at supporting cancer patients and their families. More than $100 million of that support has benefitted programs at the IU Simon Comprehensive Cancer Center. Those have included investments in the research of early career scientists, the field of bioinformatics and in supporting research and medical education aimed at helping cancer patients.