PARP Inhibition in Triple Negative Breast Cancer

Patients with triple negative breast cancer have inherent defects in several DNA repair pathways. These cancer cells therefore become increasing dependent on another DNA damage repair pathway called base excision repair (BER) pathway, for survival. It so happens that PARP 1(PolyAdenosine diphosphate Ribose Polymerase) is an important enzyme regulating the BER pathway.  By inhibiting PARP1, the BER pathway is inhibited leading to extreme levels of DNA damage and eventual death of cancer cells.

In an article published in the Jan 20,2011 issue of the NEJM, the addition of a PARP inhibitor Iniparib to a combination of Carboplatin and Gemzar in patients with metastatic triple negative breast cancer, resulted in superior Response Rates, median Progression Free Survival and Overall Survival. This difficult -to -treat subtype of breast cancer may soon become extinct.