How tumors escape oblivion

Tumors can proliferate by escaping failsafe programs such as apoptosis and senescence, according to Clemens Schmitt, Scott Lowe (Cold Spring Harbor Laboratory, Cold Spring Harbor, NY), and colleagues. Although the disabling of apoptosis was well established as an escape mechanism during tumor development, the incapacitation of the senescence pathway is now shown to be an important predictor of response to drug therapy.

Lowe and colleagues first examined which functions of p53 are needed to suppress tumor development in mice. They found that a complete block of apoptosis (using a dominant apoptosis inhibitor) removed all selective pressure of pretumorigenic cells to lose p53, and could reproduce the aggressive growth phenotype normally seen after p53 loss. This suggests that other p53-related phenotypes, such as aneuploidy and defective cell cycle checkpoints, are unimportant byproducts of p53 loss. “To those...