- PARP inhibitor enhances DNA breaks induced by TAS102, causing cancer cell death
- Findings supported current phase 1 clinical trial for refractory GI cancers
- Study published online in Cell Reports Medicine
BUFFALO, N.Y. — A preclinical study led by a team of researchers at Roswell Park Comprehensive Cancer Center highlights the potential of a novel two-drug treatment strategy targeting p53-mutant cancers. The findings, recently published in Cell Reports Medicine, lay the groundwork for further research, including a phase 1 clinical trial of colon cancer patients that is currently underway.
“Colorectal adenocarcinoma and pancreatic ductal adenocarcinoma are among the leading causes of cancer-related deaths in the United States,” notes study co-author Christos Fountzilas, MD, FACP, Co-Leader of the Gastrointestinal Disease Team and Associate Director for Solid Tumors, Early Phase Clinical Trials Program at Roswell Park. “While the tumor suppressor p53 is inactivated in most cancers, including colorectal and pancreatic, there are no FDA-approved treatments targeting mutant p53, and the p53 status of the tumor is not taken into consideration when formulating a treatment plan for the patient.”
Recognizing the need for better therapeutic options, Dr. Fountzilas and his colleague, Andrei V. Bakin, PhD, Associate Professor of Oncology, Department of Cancer Genetics and Genomics at Roswell Park, initiated a research effort to address the gap. Dr. Bakin, co-author of the study, explains that the research team investigated DNA repair upon challenge with thymidine analogs incorporated into genomic DNA during replication, hoping to better understand DNA differences in cancer and normal cells. They discovered that p53-mutant cancer cells accumulate DNA breaks due to post-replicative removal of thymidine analogs. The data show that suppressing the PARP protein, which enables cancer cells to repair themselves, enhances DNA damage induced by thymidine analogs,…
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