Abstract 5487: Synergy between FAK and PI3K inhibitors in cervical and pancreatic cancer cells

Abstract The Ras/PI3K/ERK signaling network is frequently mutated in many cancer types including cervical cancer and pancreatic cancer. Our previous study suggested that PI3K and FAK form a positive feedback loop to modulate ERK activation. We tested combined inhibition of FAK and PI3K on the growth of cervical and pancreatic cancer in vitro. We found that FAK and PI3K inhibitors synergistically inhibited the growth of some cervical cancer and pancreatic cancer cell lines. The synergy was due to both increased apoptosis and decreased cell proliferation. Molecularly, FAK inhibition caused downregulation of PI3K and ERK signaling in cervical cancer but not pancreatic cancer cells. Interestingly, PI3K inhibitors induced activation of several RTK including insulin R and IGF-1R in cervical cancer cells, as well as EGFR, Her2, Her3, Axl, and EphA2 in pancreatic cancer cells. Together, our results show the promise of combining FAK and PI3K inhibition for cervical cancer and pancreatic cancer treatment, but biomarkers for sensitivity to the combination are needed, and concomitant RTK inhibition may be required to combat potential resistance to the combination. Citation Format: Chao-Cheng Chen, Suyang Wang, Jr-Ming Yang, Chuan-Hsiang Huang. Synergy between FAK and PI3K inhibitors in cervical and pancreatic cancer cells. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5487.