Dr. Hassan on the Mechanism of Action of Talazoparib in TNBC

Saima Hassan, MD, PhD, FRCSC, a principal scientist and surgical oncologist at Centre de Recherche du CHUM, and an assistant professor in the Department of Surgery, Faculty of Medicine at Université de Montréal, discusses the mechanism of action of talazoparib (Talzenna) in triple-negative breast cancer (TNBC).

One of the mechanisms of action of talazoparib is synthetic lethality, which is how the agent functions in a BRCA-mutant setting, according to Hassan. If there are 2 hits and the inhibition of PARP, a problem exists within the homologous recombination capacity that leads to genomic instability and cell death.

However, in the case of BRCA wild-type TNBC, dysfunction of BRCA1 through other mechanisms, homologous recombination defects, or other elements of BRCAness, could be present, Hassan says. Moreover, the PARP DNA trapping that is involved could help to explain 1 of the agent's mechanisms, in which there could be efficacy in a BRCA wild-type setting, Hassan concludes.