Brigatinib Enhances PARP Inhibitors for Ovarian Cancer

Researchers at Mayo Clinic have found that the lung cancer drug Brigatinib can improve the effectiveness of PARP inhibitor treatments for high-grade serous ovarian cancer (HGSOC). The study, published in Science Advances, reveals that Brigatinib blocks an early survival response in cancer cells that typically limits the efficacy of PARP inhibitors. This mechanism involves the dual inhibition of FAK and EPHA2 tyrosine kinases, which disrupts the stability of the FRA1 transcription factor, a key driver of cancer cell adaptation. This approach was effective in preclinical models, including patient-derived xenografts, and was observed at clinically achievable concentrations of Brigatinib, regardless of the tumor's homologous recombination status. The findings suggest a potential strategy to overcome drug resistance and improve survival rates for Ovarian cancer patients, particularly those with tumors overexpressing FAK and EPHA2. Further preclinical and clinical trials are planned to validate these results.