Ovarian cancer, the second deadliest gynecological malignancy, necessitates the identification of novel therapeutic targets. Focal adhesion kinase (FAK), a non-receptor tyrosine kinase, has emerged as a promising target for ovarian cancer treatment owing to its diverse regulatory roles. While existing research has demonstrated FAK’s role in tumor progression and angiogenesis, substantial knowledge gaps remain concerning the precise mechanisms through which FAK inhibitors hinder tumorigenesis and their specific roles in anti-angiogenic processes. This study utilized bioinformatics analysis to examine FAK expression in ovarian cancer, with validation performed using clinical samples from platinum-sensitive and platinum-resistant patients. The anti-tumor effects of FAK inhibitors were investigated through in vitro and in vivo experiments. Human induced pluripotent stem cells (hiPSCs) were differentiated into endothelial cells to facilitate vascular research. Pharmacological inhibition and genetic knockdown techniques were employed to study FAK’s role in angiogenesis, followed by functional assays to analyze specific angiogenesis processes. Bioinformatics analysis identified increased FAK expression in ovarian cancer tissues, which was significantly associated with poor prognosis. Clinical specimens confirmed higher levels of total FAK and pY397 FAK in platinum-resistant cancers compared to sensitive counterparts. In vivo experiments, including laser speckle contrast imaging and CD31 immunofluorescence, demonstrated that FAK inhibitors suppress tumor angiogenesis. Both pharmacological and genetic approaches revealed a pivotal regulatory function of FAK in angiogenesis. FAK inhibition appeared particularly effective in disrupting endothelial sprouting processes across the tested models. The results provide compelling experimental evidence supporting FAK inhibitors as potential targeted therapeutic agents for ovarian cancer. Our findings suggest that the anti-tumor effects of FAK inhibitors are closely associated with the suppression of tumor angiogenesis, which may be attributed to the potent inhibitory impact of FAK blockade on endothelial sprouting. This reveals a distinct mechanism of action that differs from traditional cytotoxic agents.
Shen et al. (Fri,) studied this question.