(A-C) A) Drug sensitive cancer cells. The mechanism of YAP/TAZ activation in response to molecularly targeted therapies involves cell-autonomous events (B), such as cytoskeletal rearrangements leading to increased mechanosensitivity, as well as cell extrinsic events (C), such as remodeling of the extracellular microenvironment. Possibly, these two mechanisms cooperate to induce YAP/TAZ nuclear accumulation in cancer cells, leading to uncontrolled cell survival and proliferation in spite of drug administration.