P63 and P73 Activation in Cancers with p53 Mutation

The members of the p53 family comprise p53, p63, and p73, and full-length isoforms of the p53 family have a tumor suppressor function. However, p53, but not p63 or p73, has a high mutation rate in cancers causing it to lose its tumor suppressor function. The top and second-most prevalent p53 mutations are missense and nonsense mutations, respectively. In this review, we discuss possible drug therapies for nonsense mutation and a missense mutation in p53. p63 and p73 activators may be able to replace mutant p53 and act as anti-cancer drugs. Herein, these p63 and p73 activators are summarized and how to improve these activator responses, particularly focusing on p53 gain-of-function mutants, is discussed.

Automated summary

p53 family members p53, p63, and p73 have tumor suppressor function, but p53 has a high mutation rate in cancers causing loss of its function. This review discusses drug therapies for nonsense and missense mutations in p53, and proposes p63 and p73 activators as potential anti-cancer drugs to replace mutant p53. Strategies to improve the response of these activators, particularly for p53 gain-of-function mutants, are also discussed.