tumor-suppressor gene

If an oncogene is a stuck accelerator, a tumor-suppressor gene is the brake. Its normal job is to slow or stop cell division, repair damaged DNA, or push a dangerously abnormal cell toward self-destruction. As long as the brakes work, a cell that starts to misbehave can be reined in.

Tumor-suppressor genes encode proteins that guard the cell cycle, sense DNA damage, and trigger orderly cell death when needed. Well-known examples include p53, RB1 (behind retinoblastoma), and BRCA1 and BRCA2. Losing their function removes a layer of protection and lets damaged cells keep dividing.

Because these genes protect us, the cancer-promoting event is usually loss-of-function: the gene is silenced, deleted, or mutated so its protein no longer works. As a rule of thumb, both copies of a tumor-suppressor gene must be knocked out before protection is lost, an idea captured by the two-hit hypothesis. This contrasts with oncogenes, where a change in one copy can be enough.