Inhibition of the src oncogene: Therapeutic potential in ovarian carcinoma

Src, a non-receptor tyrosine kinase, is the convergence point for multiple cellular pathways vital for tumorigenesis. It is a key regulator of angiogenesis with indirect effects exerted through VEGF. Additional potent pro-angiogenic cytokines such as IL-6 and IL-8 act via Src as well. Src also directly affects vascular permeability by impacting endothelial cadherin function, thereby inducing vascular leakage of tumor and interstitial fluid. Furthermore, with downstream targets such as FAK, Src orchestrates cell migration and integrin functions, which collectively contribute to the metastatic phenotype. Overexpression of Src is associated with advanced ovarian cancers, and the role of chemoresistance is of special interest as Src inhibition appears to reverse platinum-resistance, in part, by upregulation of caspase-3-mediated apoptosis. Src is an attractive target in ovarian cancers, and current trials using various Src inhibitors are underway.