Understanding the Mechanism of Action Behind PARP Inhibitors for Prostate Cancer

In the treatment of prostate cancer, PARP inhibitors can lead to double-strand DNA breaks, thus resulting in cancer death, and expert said.

With prostate cancer cells, PARP inhibitors can selectively target pathogenic DNA damage repair mutations such as BRCA1 and BRCA2 to potentially improve the control of a patient’s cancer, said Michael Lai, ARNP, Fred Hutchinson Cancer Center Teaching Associate in the Division of Hematology and Oncology at the University of Washington School of Medicine. Some PARP inhibitors include olaparib (Lynparza), rucaparib (Rubraca), and niraparib (Zejula).

At the recent 8th Annual School of Nursing Oncology, Lai presented on the optimized use of PARP inhibitors in the treatment of patients with prostate cancer. He also spoke with Oncology Nursing News to understand the mechanism of action of PARP inhibitors and how they can further benefit patients.

Transcript:

The PARP inhibitor class of drugs work by inhibiting the PARP protein, which is an enzyme involved in single-strand DNA repair. By inhibiting PARP, this can lead eventually to double-strand DNA breaks.

Now, typically, a normal cell without any issues in its DNA repair will rely on the powerful homologous recombination repair process to address double-strand DNA breaks and perform then the needed DNA damage repair to survive. But if you have a cell with a key mutation in homologous recombination repair, particularly BRCA1 or BRCA2, then without this machinery in play, using a PARP inhibitor at that time, thereby also shutting down this avenue for single-strand DNA repair, can essentially open up a lethal vulnerability and result in cancer cell death.

So specifically in prostate cancer cells, we can selectively target those with known pathogenic DNA damage repair mutations like BRCA1 and BRCA2, and hopefully better control patients’ cancer.

This transcript has been edited for clarity.