Knudson's two-hit hypothesis

Knudson's two-hit hypothesis explains how certain cancers, like retinoblastoma, develop due to two genetic changes, or "hits," in a tumor suppressor gene. Normally, these genes help prevent uncontrolled cell growth. If one copy of the gene is damaged (first hit), the other may still function. However, if a second hit damages the remaining healthy copy, the gene loses its protective ability. This loss of function allows cells to grow uncontrollably, leading to cancer. The hypothesis highlights that both copies of a tumor suppressor gene must be inactivated, often through different mutations, for cancer to occur.