Cancer progression and p53

Abstract

In a complex organism, somatic cells are under intermittent selection pressure for the emergence of mutants that can survive environmental insults and that can grow autonomously despite adverse conditions. Repeated rounds of mutation, selection, and proliferation may lead to cancer. The organism prevents malignant transformation by assuring accurate DNA repair before cell division, by forcing the death of cells with excessive DNA damage, and by placing limits on the replicative lifespans of most somatic cells. The p53 gene is a "guardian of the genome"--it regulates multiple components of the DNA damage control response and promotes cellular senescence. Disabling mutations and deletions of p53 occur in 50% of human tumours. p53-deficient cancers are often unstable, aggressive, and resistant to therapy.