Re-thinking preclinical models of cancer metastasis

Cell migration is a key step within the metastatic cascade and is the leading cause of death in cancer patients. Classically, focal adhesions are required at the leading edge of a motile cell. Wherein, focal adhesion formation requires the coordinated action of integrins, scaffolding, cytoskeletal regulators, and kinases. Src, the prototypical oncogene is known to facilitate adhesion formation by forming a signaling module with FAK. Because of this, Src has been the target of recent small molecule inhibitors. Our recent work however, shows that Src is differentially required in cells undergoing adhesion-independent migration. Thus, providing a possible explanation for the lack of efficacy observed in Src inhibitor clinical trials