Andrew W. Brotman, MD Executive Vice President and Vice Dean for Clinical Affairs and Strategy, Chief Clinical Officer | NYU Langone Hassenfeld Children's Hospital
Andrew W. Brotman, MD Executive Vice President and Vice Dean for Clinical Affairs and Strategy, Chief Clinical Officer | NYU Langone Hassenfeld Children's Hospital
A recent study conducted by scientists at NYU Langone Health has provided new insights into the role of the BRCA2 gene in cancer cell response to PARP inhibitors, a class of precision cancer drugs. According to the research, the gene determines how effectively PARP inhibitors can kill cancer cells.
The study, published in Nature, addresses the continuous DNA damage in human cells during division and growth, which must be repaired to prevent cancer. BRCA2 plays a crucial role in this repair mechanism, but mutations can compromise this function, increasing cancer risk. Cancer cells with compromised BRCA2 rely on the poly ADP-ribose polymerase 1 (PARP1) pathway for DNA repair, which PARP inhibitors are designed to block.
The research discovered an unexpected function of BRCA2 in managing PARP1 action at DNA damage sites, explaining why PARP inhibitors work only in some patients. "This work is part of a larger effort across NYU Langone and Perlmutter Cancer Center to connect molecular discovery with clinical advances," said Eli Rothenberg, PhD, the study's senior author. He emphasized their goal of translating insights into actionable diagnostics and treatment strategies.
To further understand the interaction between BRCA2 and PARP1, NYU Langone researchers employed proprietary imaging techniques. "This finding would not have been possible without the specialized imaging tools pioneered by the Single Molecule Biophotonics program here," Rothenberg noted. These tools provided a "molecular window into how BRCA2 protects DNA repair complexes from disruption."
Their findings showed that BRCA2 acts as a shield, preventing PARP1 from blocking DNA repair sites, allowing RAD51—a crucial repair protein—to function. In cases where BRCA2 is defective, PARP1 inhibits RAD51 access, leading to the vulnerability of BRCA2-deficient tumor cells to PARP inhibitors.
First study author Sudipta Lahiri, PhD, mentioned the team's focus on clinical applications of this mechanism, highlighting the need for "patient-specific tumor profiling," potentially enhancing therapy selection. The study was co-authored by researchers from NYU Langone Health and the Yale School of Medicine, with funding from the National Institutes of Health, the National Cancer Institute, and several foundations.
NYU Langone Health, renowned for its integration and quality care, consistently ranks highly in various medical specialties and operates numerous medical and research facilities in the New York area and Florida.
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