Lung Cancer Drug Brigatinib Shows Promise in Enhancing Ovarian Cancer Treatment

Mayo Clinic researchers in Rochester have discovered that Brigatinib, an FDA-approved lung cancer drug, can enhance the effectiveness of PARP inhibitors in treating aggressive ovarian cancer. The study, published in Science Translational Medicine, reveals that the drug can block survival pathways that cancer cells activate to resist treatment.

PARP inhibitors are a common therapeutic option for the treatment of high-grade ovarian cancer and can be effective in cancers with impaired DNA repair. However, the research found that ovarian cancer cells rapidly activate a survival mechanism following treatment with PARP inhibitors, which are designed to exploit weaknesses in cancer cell DNA repair mechanisms.

Graduate student Julie Duffield, one of the main authors on the study, found that cancer cells can create defensive mechanisms against PARP inhibitors by activating a gene that allows the cells to avoid death. The team worked on a similar class of drugs that belong to Brigatinib and found that Brigatinib combined with PARP inhibitors is an effective form of treatment without harming healthy cells.

An assistant professor of pharmacology and author of the study said he was most surprised by how quickly these ovarian cancer cells activate their defense mechanism after starting treatment with PARP inhibitors. PARP inhibitors inhibit DNA repair, which is essential for repairing all the DNA damages, and Brigatinib blocks a survival pathway that ovarian cancer cells activate immediately after PARP inhibitor treatment begins.

By blocking this adaptive survival response, researchers propose it may be possible to prevent resistance and improve patient outcomes. The study is in a pre-clinical stage. Researchers plan to partner with doctors for a clinical trial to test safety and efficacy in patients.