Exploiting signaling rewiring in cancer cells with co-existing oncogenic drivers.

The development of tailored therapies designed to specifically target driver oncogenes has initiated a revolutionary era in cancer biology. The availability of a growing number of selective inhibitors has generated novel experimental and clinical paradigms. These represent an opportunity and a challenge for researchers and clinicians to delve deeper into the intricate dynamics of cancer development and response to treatment. By directly inhibiting key driver oncogenes involved in tumor initiation and progression, scientists have an unprecedented opportunity to conduct longitudinal and clonal evolutionary studies of how cancer cells adapt, rewire, and exploit conflictive or overlapping signaling dependencies in response to treatment in vitro and in vivo. This challenge has to be progressively resolved to discover more effective and personalized cancer therapies.