COLUMBUS, Ohio – A study led by The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James) found clinical efficacy of a new therapy to treat chronic lymphocytic leukemia (CLL) that has stopped responding to other therapies. Jennifer Woyach, MD, director of hematology at the OSUCCC – James, was co-senior and corresponding author for the study published in Blood Cancer Discovery, a journal of the American Association for Cancer Research. Britten Gordon, PhD student in the Biomedical Sciences Graduate Program and a Pelotonia Scholar at the OSUCCC – James, was first author. What is CLL? CLL is the most common leukemia in adults with the average age of diagnosis being 70. Treatment options for CLL have evolved over the years to include therapies that target cancer cells that have grown resistant to certain therapeutics. In the last few years, Woyach and the team at Ohio State have played a vital role in the research and development of these therapies—ibrutinib, acalabrutinib and pirtobrutinib—which are also known as Bruton's tyrosine kinase inhibitors (BTKi). This study analyzed a new drug, MS-553, and its ability to target a protein called PKCβ to treat CLL, especially in cases where the disease is resistant to current treatments. Like BTKi treatments, MS-553 targets CLL signaling and can stop or kill a population of CLL cells. “Many patients with CLL eventually stop responding to BTK inhibitors due to mutations in the cancer cells, and it’s important that we continue to find new ways to treat these patients,” said Woyach, also a professor at Ohio State College of Medicine. “Our study showed that in the laboratory MS-553 was effective in multiple models of CLL including those with resistant disease, and we think this is likely to translate to the clinic as well.” How does MS-553 work? MS-553 is a selective inhibitor of PKCβ and targets CLL cells without harming normal immune cells. In this study, the researchers tested the drug in lab models (cell lines, patient samples and mice) to see if it could kill CLL cells and block the signals that help these cells survive. In mouse models, MS-553 slowed disease progression and improved survival. Further, MS-553 was found to be effective even in CLL cells with mutations that make them resistant to both covalent and non-covalent BTK inhibitors. “When combined with venetoclax, MS-553 makes CLL cells even more sensitive to treatment,” said Gordon. “Our study supports further clinical testing of MS-553 for patients with drug-resistant CLL.” Other study co-authors include researchers from Ohio State, The University of Texas MD Anderson Cancer Center, and the University of Cincinnati. To learn more about cancer treatment and clinical trials at the OSUCCC – James, visit cancer.osu.edu or call 1-800-293-5066. Media Contact: Mary Ellen Fiorino, Mary.Fiorino@osumc.edu