Beyond the Oncogene Revolution: Four New Ways to Combat Cancer

It has become clear that tumorigenesis results from much more than just the activation of an oncogene and/or the inactivation of a tumor-suppressor gene, and that the cancer cell genome contains many more alterations than can be specifically targeted at once. This observation has led our group to a search for alternative ways to kill cancer cells (while sparing normal cells) by focusing on properties unique to the former. We have identified four approaches with the potential to generate new anticancer therapies: combatting the tactics by which cancers evade antitumor immune responses, targeting metabolic adaptations that tumor cells use to survive conditions that would kill normal cells, manipulating a cancer cell's response to excessive oxidative stress, and exploiting aneuploidy. This review describes our progress to date on these fronts.