BIM-mediated apoptosis and oncogene addiction.

Oncogene addiction is a phenomenon whereby suppression of a driver oncogene is associated with dramatic tumor regression that has been observed in experimental models and in response to targeted therapies [1]. However, the mechanism by which oncogene inactivation induces this massive reduction in tumor burden is not clear. In tumors addicted to the MYC oncogene, suppression of this oncogene leads to tumor regression that is associated with a marked increase in apoptosis. This at first glance appears to be paradoxical since generally oncogene activation, and MYC activation in particular, is associated with increased apoptosis. Recently, we have described a possible mechanism that may explain why inactivation of pro-apoptotic oncogenes, such as MYC, induce apoptosis [2].