Dr. Hussain on the Rationale to Target the DNA Repair Pathway in mCRPC

Maha Hussain, MD, FACP, FASCO, Genevieve E. Teuton Professor of Medicine, Division of Hematology and Oncology, Department of Medicine, Deputy Director, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, discusses the rationale for targeting the DNA repair pathway in metastatic castration-resistant prostate cancer (mCRPC).

Previously reported data revealed that more than 20% of patients with mCRPC harbor mutations in the DNA repair pathway or homologous recombination (HRR) genes, Hussain says.

Additionally, targeting the DNA damage repair pathway has demonstrated success in other tumor types, including breast cancer, ovarian cancer, and pancreatic cancer, explains Hussain.

The rationale to target this pathway stems from the fact that all damaged cells, including cancer cells, need to repair themselves, Hussain says. The HRR pathway, which is involved in the repair process, cannot function properly in the presence of mutations.

When the cells are unable to repair themselves, they go to the PARP pathway, Hussain explains.

As such, PARP inhibitors, such as olaparib (Lynparza), which was evaluated in the phase 3 PROfound trial, inhibit the PARP enzyme to further prevent cells from repairing themselves, concludes Hussain.