Change or die: Targeting adaptive signaling to kinase inhibition in cancer cells

Small molecule kinase inhibitors have proven enormously successful at delivering impressive responses in patients with cancers as diverse as chronic myeloid-leukemia, melanoma, breast cancer and small cell lung cancer. Despite this, resistance is commonplace and most patients ultimately fail therapy. One emerging observation is the rapid rewiring of signaling that occurs across multiple cancer types when driver oncogene function is inhibited. These adaptive signaling changes seem critical in delivering some of the earliest survival signals that allow small numbers of cells to evade therapy. In this commentary we review the mechanisms that contribute to the robustness of signaling networks within cancer cells and suggest new therapeutic strategies to limit treatment failure.