tumorsuppressor

Tumor suppressor, in the context of genetics and cancer biology, refers to genes whose protein products help prevent uncontrolled cell growth and maintain genomic stability. They act as brakes on cell division, participate in DNA repair, promote apoptosis or cellular senescence in response to damage, and help preserve chromosomal integrity. When tumor suppressor function is lost or inactivated, cells are more likely to accumulate mutations and progress toward cancer.

A central concept is the two-hit hypothesis, which posits that both alleles of a tumor suppressor gene typically must be inactivated for tumorigenesis to proceed. This can occur through somatic mutations, chromosomal deletions, or epigenetic silencing; germline mutations can predispose individuals to cancer, with a second hit often occurring somatically. Some genes can also contribute to cancer when haploinsufficient or through dominant-negative effects.

Key examples include TP53 (p53), RB1, PTEN, BRCA1, BRCA2, APC, NF1, NF2, VHL, and CDKN2A. p53 coordinates responses to DNA damage and stress, leading to cell cycle arrest or apoptosis; RB1 governs the G1 to S phase transition; BRCA1/2 are essential for homologous recombination repair; PTEN antagonizes PI3K/AKT signaling; APC regulates Wnt signaling.

Clinical relevance includes predisposition to hereditary cancer syndromes such as Li-Fraumeni (TP53), familial retinoblastoma (RB1), and familial adenomatous polyposis (APC). Therapeutically, strategies exploiting tumor suppressor loss—such as synthetic lethality with PARP inhibitors in BRCA-mutant cancers—are actively developed, while efforts to restore or compensate for tumor suppressor activity continue in research.