Rosa Lapalombella, PhD, assistant professor of Internal Medicine; Robert Baiocchi, MD, PhD, associate professor of Internal Medicine; and John Byrd, MD, D. Warren Brown Chair of Leukemia Research, professor of Medicine and Medicinal Chemistry at The Ohio State University College of Medicine, received a $2.3 million award from the National Cancer Institute, a division of the National Institutes of Health. The grant, “Targeted therapies for Richter's transformation,” explores ways to discover novel targeted therapeutic strategies for translation into clinical trials for patients with Richter’s transformation. Funding for the series of studies will extend through January 2022.
Richter's transformation (RT) is an aggressive, incurable blood cancer that arises when the most common leukemia, chronic lymphocytic leukemia (CLL), makes the transition to a high-grade lymphoma. The Ohio State research team’s preliminary data and previously published work identifies BRD4 and PRMT5 proteins to be essential for the development of lymphoma. Shown by laboratory and preclincal animal models of RT, drugs can block the function of BRD4 and PRMT5 proteins.
The Ohio State research team wants to figure out how BRD4 and PRMT5 contribute to development of RT. Their overall goal is to develop novel markers that can predict RT development and discover innovative therapy strategies.
The outcome of the project will enable the Ohio State team to utilize a highly novel, integrated, epigenomic approach to mechanistically address how BRD4 and PRMT5 contribute toward global epigenetic changes favoring the emergence of the RT clone.
“Here at The Ohio State University Comprehensive Cancer Center, we have excellent basic scientists and translational investigators in both CLL and lymphoma to address the biology of Richter’s transformation and come up with rational treatment strategies that we can test in the preclinical setting. This, together with our access to patients’ samples, novel mouse models we have established and first-in-class drugs, will help us to make an important contribution to this disease.”
Currently Richter’s transformation is treated with chemotherapy, which is not particularly effective. “By studying signaling pathways that are important, we hope to make targeted therapies an effective treatment for this disease.”
“We hope that our preclinical evaluation will lead to a new clinical trial where we can target BRD4 and PRMT5 in this patient population.”
The co-investigators on the grant are Amy Lehman, MAS; Christopher Oakes, PhD; Hatice Ozer, PhD; and Deepa Sampath, MD.