PARP Inhibitors: The Move Towards Genetic Targeted Treatment for Prostate Cancer

Dr. Daniel P. Petrylak, MD spoke of poly(ADP-ribose) polymerase (PARP) inhibitors having the potential to change the standard of care for prostate cancer (PCa) at the 13th Annual Interdisciplinary Prostate Cancer Conference and Other Genitourinary Malignancy Conference in 2020. His talk raised a few questions:¹

• What is PARP?
• What role does it play in fighting prostate cancer?
• Who will benefit from this new treatment method?

What is PARP?

PARP is short for poly(ADP-ribose) polymerase. It is a protein found in cells. It helps damaged cells repair their DNA (genetic building blocks of all life). The PARP protein is usually a good and useful thing, repairing mutated cells.^2,3

In fact, cancer cells are susceptible to DNA damage. That is why experts like Dr. Petrylak are studying the PARP protein to see if it can be used to stop (inhibit) the cancer cell growth.^2,3

PARP as targeted therapy

PARP inhibitors a class of drugs known as targeted therapy or precision medicine. Targeted therapy means the drug attacks or disrupts a specific function in the cancer cells. The hope is that targeted therapy will spare healthy cells, cause fewer side effects, and inhibit cancer cell growth better than other treatments.^2,4

Experts initially focused their research into PARP inhibitors on breast and ovarian cancers, especially those people with faulty BRCA1 and BRCA2 genes. There was a good reason for this. These genes, like PARP, are responsible for cell repair. When BRCA genes are faulty they no longer repair cells, which can increase the risk of certain cancers. Research focused on PARP inhibitors' ability to stop cancer cells from repairing themselves.^2,4

PARP for prostate cancer

People with prostate cancer also may have a BRCA mutation. That is why experts are turning what they learned about PARP inhibitors for other cancers to prostate cancer. (You are not alone in thinking treatments seem to be developed for other cancers and only tested for PCa later.) At this point, there are 2 FDA-approved PARP inhibitors for treating prostate cancer: Rucaparib (Rubraca) and Olaparib (Lynparza). Several others are being studied in clinical trials.⁵

Olaparib (Lynparza) was first approved to treat breast and ovarian cancer. Then it was given FDA Breakthrough Designation for BRCA1 and BRACA2 mutated castration-resistant prostate cancer. People who got Olaparib had a 66 percent reduction in disease progression compared to Zytiga or Xtandi plus prednisone.^6,7

Niraparib (Zejula) has also been given Breakthrough Designation and has gone through phase II trials. Early results have been encouraging.⁸

Of course, not all people with metastatic prostate cancer have these genetic mutations. But, about 20 percent to 22 percent do. That’s why doctors prescribe drugs that damage cancer cells' DNA such as platinum chemotherapy or PARP inhibitors.⁶

How else can these newer treatments help?

There is a chance that PARP inhibitors may be combined with other treatments to help those prostate cancer who do not have faulty DNA repair genes. For example, experts are studying whether drugs called androgen receptors may be used with PARP inhibitors to treat prostate cancer at different stages.^5,8

These treatment advances show that hereditary and tumor-specific genetic testing and counseling may help doctors identify people with inherited forms of cancer earlier, and that PARP inhibitors may help more of them.⁶