The Idea Grants are funded by the OSUCCC – James Intramural Research Program (IRP), which receives extensive support from Pelotonia and other sources. This funding is extremely helpful to these teams because it is difficult to acquire grant funding from the NCI and other outside sources for projects that are still in early development.
Since 2010, the OSUCCC – James has awarded 175 Idea Grants totaling $20.9 million for more than 180 investigators across nine of the 15 colleges at Ohio State, as well as at Nationwide Children’s Hospital and Cincinnati Children’s Hospital Medical Center. These competitive awards provide support for two years and for up to $200,000 each.
“These grants enable our scientists to build momentum for moving their emerging ideas forward into research projects that stand a better chance of landing external funding,” says OSUCCC director Raphael E. Pollock, MD, PhD, FACS. “Our community of Pelotonia participants — including riders, virtual riders, volunteers, donors, corporate sponsors and everyone who this year contributed through personal My Pelotonia activities — should take pride in helping to fund Idea Grants that ultimately advance cancer research.”
The latest round of IRP-funded Idea Grants, awarded in July, consists of nine grants totaling $1.5 million. Eight of these grants received Pelotonia support and one received support from the Stefanie Spielman Fund for Breast Cancer Research at the OSUCCC – James.
On the next three pages are summaries of these nine awards. Each summary is listed with the project title, the associated team of investigators, and the OSUCCC – James research program with which each investigator is affiliated, if applicable. An asterisk beside a name indicates that person is the “contact” principal investigator.
Adipose Tissue Contributions to Pancreatic Cancer Development
Investigators: Martha Belury, PhD, Molecular Carcinogenesis and Chemoprevention (MCC) Program; Joshua Blakeslee, PhD; Zobeida Cruz-Monserrate, PhD*, MCC Program; Mary Dillhoff, MD, Translational Therapeutics (TT) Program; Terence Williams, MD, PhD, Cancer Biology (CB) Program
Obesity is a risk factor for developing pancreatic cancer. This team will determine whether adipose (fatty) tissue affects the pancreatic cancer tumor components that can contribute to promoting cancer development, progression and tumor growth. The team will then develop strategies to identify obese individuals who are at risk of developing pancreatic ductal adenocarcinoma (PDAC). Study results will provide insights to guide new preventive, early detection and treatment approaches to obesity-associated pancreatic cancer.
Platelet-Derived Growth Factor-B as a Metastasis Promoter in Breast Cancer
Investigators: Vincenzo Coppola, MD, and Gina Sizemore, PhD*, both of the CB Program
Women diagnosed with breast cancer-associated brain metastases (BCBM) have an unacceptable median overall survival rate of 10-11 months. A major knowledge gap in the BCBM field is the functional interplay between tumor cells and the metastatic brain tumor microenvironment. This proposal will test whether mammary epithelial expression of the paracrine mediator, platelet-derived growth factor-B (PDGFB), promotes breast cancer progression with a propensity for brain metastatic spread. Completion of this work could improve survival for women whose tumors exhibit enhanced PDGFB signaling by providing insight for novel prognostic and therapeutic strategies.
(Note: This project was funded by IRP money from the Stefanie Spielman Fund for Breast Cancer Research at the OSUCCC – James.)
Senolytic Agents as Mitigators of Delayed Radiation Toxicities
Investigators: Rajeswara Rao Arasada, PhD; Naduparambil Jacob, PhD*, TT Program; Xiaokui Mo, PhD
Some lung cancer patients receive ionizing radiation as a main treatment modality, as it causes DNA double strand breaks that kill cancer cells. However, injury to normal tissue in the exposure field is unavoidable, causing such undesirable side effects as radiation pneumonitis and chronic radiation fibrosis. These effects can be particularly significant in the lungs, which are highly susceptible to inflammation and scarring. Increasing treatment-failure rates in lung cancer patients are attributed to the aggressiveness of this disease, which necessitates treatment with high doses of radiation that result in toxicities that are exacerbated by age. Cellular senescence or irreversible cell cycle arrest is linked with aging, and radiation injury worsens the aging process. Moreover, senescent cells accumulated in radiation-exposed lungs secrete factors that cause inflammation. This team will optimize novel strategies to clear senescent cells from the lungs, thus rejuvenating healthy surrounding tissue and improving organ health. They also propose novel blood-based diagnostics for early detection of senescent cells and lung inflammation, which will help guide timely mitigation.
A Trial of Long-Chain Omega-3 Fatty Acids in a Murine Model of Complex Atypical Endometrial Hyperplasia
Investigators: Theodore Brasky, PhD*, Cancer Control (CC) Program; Takeshi Kurita, PhD, CB Program (co-PI); Martha Belury, PhD, MCC Program; David Cohn, MD, MBA, TT Program; Erinn Hade, PhD; and Joseph McElroy, PhD
Endometrial cancer is the most common gynecologic cancer and the fourth most common cancer among women. With increasing incidence rates, preventive strategies are needed. Chronic inflammation is thought to be important in endometrial cancer development, and there is evidence that anti-inflammatory agents may reduce risk. Long-chain omega-3 polyunsaturated fatty acids, which derive mainly from diets high in oily fish and fish oil supplements, hold anti-inflammatory properties and may reduce endometrial cancer occurrence. Results from Dr. Brasky’s large studies in women indicate that omega-3 fatty acids may reduce endometrial cancer occurrence by 20%. The team’s objective here is to generate preclinical data to support a future prevention trial among women, based on the hypothesis that omega-3 fatty acid-enriched diets will increase the concentration of fatty acids in the uterus and reduce markers of uterine inflammation. To test this, they will use Dr. Kurita’s newly developed mouse model, which mimics the most common genetic mutations in early-stage endometrial cancer. The six-month trial supported by this Idea Grant will involve 52 mice randomized to an omega-3 enriched diet or a control diet. After the trial, uterine tissues will be removed and analyzed for fatty acid content and inflammation. This study could provide data needed to apply for an NIH grant to perform a trial of omega-3 supplementation in women for endometrial cancer.
Zebrafish Models to Characterize OCA2 Skin Cancer Risk Variants
Investigators: Bradley Blaser, MD, PhD, LR Program, and Amanda Toland, PhD*, MCC Program
Variations in the OCA2 gene that determine eye and skin color increase the risk for skin cancer. Dark pigment decreases skin cancer risk via protection from sun-induced mutations. There is new evidence that OCA2 may be protective for skin cancer beyond its role in pigment. This team will use zebrafish to test this by characterizing the impact of OCA2 DNA variants found in patients on pigment levels, melanoma development and other tumor-related phenotypes, such as blood vessel growth. These data will provide evidence that loss of OCA2 impacts melanoma development and will inform studies to prevent and treat OCA2-related skin cancers.
A Pilot Phase I Trial of IL-21 Expanded, Off-the-Shelf, Third-Party Natural Killer (NK) Cells in Combination With Mogamulizumab in Patients With Cutaneous T-Cell Lymphomas or Adult T-Cell Leukemia/Lymphomas
Investigators: Basem M. William, MD*, LR Program; Catherine Chung, MD; Ying Huang; Dean Lee, MD, PhD, LR Program; Anna Vilgelm, MD, PhD, TT Program; and Sumithira Vasu, MD, LR Program
Cutaneous T-cell lymphoma (CTCL) and adult T-cell leukemia lymphoma (ATLL) are aggressive cancers that are usually incurable. This team has established a bank of natural killer (NK) cells — immune cells that have significant antitumor activity — from healthy donors. They will infuse those cells in combination with an antibody (immune protein) called mogamulizumab, which is currently approved for treating CTCL (in the United States) and ATLL (in Japan), in a pilot clinical trial of three to 12 patients with CTCL/ATLL. They expect to find that the combination of NK cells and mogamulizumab would be safe and work synergistically to kill cancer cells.
A Phase IB Dose De-Escalation Study of Atezolizumab and All-Trans Retinoic Acid in Patients With Advanced Non-Small Cell Lung Cancer
Investigators: William Carson, MD, TT Program; Gregory Otterson, MD, TT Program; Dwight Owen, MD*, TT Program; Sandipkumar Patel, MD; Robert Wesolowski, MD, TT Program
Despite recent treatment advances, the median survival for patients with metastatic non-small cell lung cancer (NSCLC) remains approximately one year. Immunotherapy with checkpoint inhibitors has led to responses and improved survival in a subset of patients with advanced NSCLC, but nearly all patients eventually need additional therapies. The optimal treatment for patients whose cancer progresses after receiving immunotherapy — either alone or in combination with chemotherapy — remains unclear, so new strategies are needed. This team will evaluate a novel combination of therapies to target a component of the immune system called myeloid-derived suppressor cells (MDSC) that can interfere with immunotherapy. Specifically, they will study all-trans retinoic acid (ATRA) to target MDSCs in combination with atezolizumab, which is an approved immunotherapy. The investigators hope this combination of therapies will improve responses in patients with NSCLC who have already received standard treatment. From blood samples collected during this clinical trial, they also hope to discern the effect of this combination on levels of immune cells in the blood and to determine whether these changes can guide therapy.
TP-0903 to Treat RAS-Mutated Relapsed/Refractory Acute Myeloid Leukemia (AML)
Investigators: Bhavana Bhatnagar, DO*, LR Program; John C. Byrd, MD, LR Program; and Kristin Koenig, MD
Patients with AML whose disease doesn’t respond to initial treatment, and those with relapsed disease, have poor outcomes following subsequent therapies. In recent years, the discovery of genetic mutations in AML has revolutionized the management of these patients. One such mutation involves the RAS gene, and 17.4% of AML patients who do not respond to their first treatment, or whose disease returns, have RAS gene mutations. AML patients with recurring disease and RAS mutations have a poor prognosis, and those with additional mutations in IDH1 or IDH2 genes fare even worse. Based on the hypothesis that elimination of the RAS mutations will improve prognosis for these patients, Bhatnagar and colleagues will conduct a clinical trial evaluating a novel oral drug called TP-0903 to determine its safety and activity in treating AML patients with RAS mutations when taken alone or in combination with other treatments (venetoclax, ivosidenib or enasidenib). The trial will be open to AML patients 18 or older who do not respond to initial treatment or who have recurrent disease. If the investigators find a safe dose of TP-0903 along with the other drugs, they can study whether these combinations improve prognosis for these patients.
Early Detection of Cardiotoxicity After Lower Thoracic Radiotherapy
Investigators: Daniel Addison, MD, CC Program; Ragavendra Baliga, MD; Arnab Chakravarti, MD, TT Program; Ning Jin, MD, TT Program; Michael Knopp, MD, PhD, TT Program; Eric Miller, MD*, PhD, TT Program; Ryan Robb; Patrick Ruz; Orlando Simonetti, PhD; Lai Wei, PhD; Terence Williams, MD, PhD, CB Program; Chadwick Wright, MD, PhD, TT Program
Radiation therapy is a primary treatment for many thoracic malignancies, including esophageal and lung cancers. Being nearby, the heart is often exposed to high amounts of radiation despite basic reduction strategies. Recent high-profile studies in lung and esophageal cancer have demonstrated cardiotoxicity events begin to occur within two years of completing radiation when patients are monitored closely. Further, recent advances in treatment have resulted in improvements in survival for patients with esophageal and lung cancer, making radiation toxicity a significant source of morbidity and mortality for survivors. As a result, cardiotoxicity, including arrhythmias, heart failure and coronary disease, has emerged as a leading cause of non-cancer deaths after radiation for these patients. There are no available tools to help identify patients at risk for or with impending signs of these heart events. This team will use cutting-edge imaging techniques and blood markers to identify early adverse changes in the heart of patients with thoracic malignancies both during radiation therapy and shortly after completing treatment. This will allow identification of patients at high-risk for cardiotoxicity and lay the foundation for a clinical trial on a preventive strategy for these potentially devastating events.