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How PARP Treats Advanced Prostate Cancer

The FDA has approved rucaparib as a treatment for men who have advanced prostate cancer with mutated BRCA1/BRCA2 genes.

Prostate cancer is the number one cancer andthe second cause of cancer deaths among men in the USA. The mCRPC (metastatic, castrate-resistant prostate cancer) is incurable, but researchers are exploring possible treatment options.

Rucaparib falls under the PARP (Poly ADP-ribose polymerase) inhibitors class. The anti-cancer drugs target cancer cells with weakness, especially on how they repair their damaged DNA. The drugs have been used to treat ovarian cancer, and some inherited types of pancreatic and breast cancer.

mCRPC patients present poor outcomes when they use conventional treatment methods. Therefore, to treat patients with advanced prostate cancer, there needs to be personalized medicine. Twelve percent of patients with advanced prostate cancer have tumors with BRCA2/BRCA1 alteration. Therefore, the rucaparib FDA approval is exciting to patients, oncologists, and researchers.

The objective of the TRITON2 PHASE II study was to find out if rucaparib can effectively and safely treat men with mCRPC due to their genetic profile. The study participants included men who had completed chemotherapy and hormone therapy. The participants were given 600mg of rucaparib two times a day. The prostate-specific antigen levels in more than half the patients improved.

The researchers concluded that the anti-cancer drug had a similar safety profile with what they had experienced in other tumors. They, however, identified anemia as the most common side effect.

Research is underway to establish test combinations of PARP inhibitors with other experimental or conventional therapies to increase the number of mCRPC patients that benefit from the PARP inhibitor.

Patnaik, MD, Ph.D., and one of the research authors explains, “In a separate publication, we have demonstrated that additional non-BRCA1/2 mutations within the DNA repair pathway in mCRPC patients could confer sensitivity or resistance to PARP inhibitor rucaparib…. We still have a lot more to learn about which patients with additional genetically defined alterations in the DNA repair pathway will benefit most from this therapy.”

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