P63 and P73 Activation in Cancers with p53 Mutation
Bi‐He Cai, Yun-Chien Hsu, Fang-Yu Yeh, Yu-Rou Lin, Rui-Yu Lu, Si-Jie Yu, Jei‐Fu Shaw, Ming-Han Wu, Yi-Zhen Tsai, Ying-Chen Lin, Zhi-Yu Bai, Yu‐Chen Shih, Yi‐Chiang Hsu, Ruo-Yu Liao, Wei-Hsin Kuo, Chao‐Tien Hsu, Ching‐Feng Lien, Chia‐Chi Chen
Abstract
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.