Abstract High grade serous ovarian cancer (HGSOC) - the most common subtype - accounts for the greatest number of patient deaths due to late detection and frequent recurrence. Treatment for HGSOC patients begins with cytoreductive surgery followed by platinum/taxane chemotherapy and adjuvant/maintenance therapy, the latter being specific to whether tumors are homologous recombination-proficient (HRP) or homologous recombination-deficient (HRD). HRD cancers are treated with PARP inhibitors (e.g. Niraparib) while HRP cancers are treated with bevacizumab, an anti-angiogenesis agent. Either regimen can be extended into maintenance therapy. Over 70% of HGSOC tumors present with amplifications or gains in the PTK2 gene that codes for the focal adhesion kinase (FAK) protein, a key regulator of tumor cell migration, adhesion, and chemotherapy resistance that also regulates the endothelial cell response to VEGF. FAK-targeting drugs have been approved for use in the clinic for the treatment of low grade serious ovarian cancer, but their role in HGSOC is less clear. We have previously shown that FAK inhibition compromises several cell survival pathways, among them, a suite of key DNA repair enzymes. Unexpectedly, we find that FAK inhibition imbues PARP sensitivity on HRP cells. In vivo, an enhanced anti-tumor effect was observed with suboptimal doses combinations of FAK and PARP inhibitors. Notably, an even greater effect was observed when combining FAK and PARP inhibitors in a maintenance therapy model for chemoresistant HGSOC. FAK inhibition through treatment with narmafotinib impacts PARP1 protein expression, cleavage, and overall PARylation levels, implicating functional interaction between FAK and PARP pathways within the cell. These results provide an unexpected avenue to evaluate PARP inhibition as a viable therapy for HRP tumors. Citation Format: Caree Carson, Breana Hill, Aarya Ghosalkar, Marjaana Ojalill, Antonia Boyer, Xiao Lei Chen, David Schlaepfer, Dwayne Stupack. Co-treatment with FAK and PARP inhibitors for the treatment of homologous recombination-proficient high grade serious ovarian cancer abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 6491.
Carson et al. (2026) studied this question.