"
Oncogene addiction" describes the curious acquired dependence of
tumor cells on an activated oncogene for their survival and/or proliferation, a phenomenon that has important implications for the success of targeted
cancer therapies. However, the mechanisms explaining
oncogene addiction remain elusive. We propose that "addiction" may be an illusion generated as a consequence of differential attenuation rates of prosurvival and proapoptotic signals emanating from an
oncoprotein acutely following its inactivation. According to this model, which we call "oncogenic
shock," prosurvival signals dissipate quickly on
oncoprotein inactivation whereas proapoptotic signals linger sufficiently long to commit the cell to an apoptotic death. This mechanism may contribute to the rapid and dramatic clinical responses observed in some
cancer patients treated with selective
tyrosine kinase inhibitors and could yield additional
drug targets that determine the balance of signaling outputs from activated
oncoproteins.