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Mutant p53 in cancer therapy—the barrier or the path
Xiang Zhou 1,†,* , Qian Hao 2,† , and Hua Lu 3
1 Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, and Key Laboratory of Medical Epigenetics and Metabolism, Fudan University, Shanghai 200032, China
2 Fudan University Shanghai Cancer Center, Fudan University, Shanghai 200032, China
3 Department of Biochemistry & Molecular Biology and Tulane Cancer Center, Tulane University School of Medicine, New Orleans, LA 70112, USA
*Correspondence to:Xiang Zhou, E-mail: xiangzhou@fudan.edu.cn
J Mol Cell Biol, Volume 11, Issue 4, April 2019, Pages 293-305  https://doi.org/10.1093/jmcb/mjy072
Keyword: mutant p53, gain-of-function, cancer therapy, chemoresistance, synthetic lethality

Since wild-type p53 is central for maintaining genomic stability and preventing oncogenesis, its coding gene TP53 is highly mutated in ~50% of human cancers, and its activity is almost abrogated in the rest of cancers. Approximately 80% of p53 mutations are single point mutations with several hotspot mutations. Besides loss of function and dominant-negative effect on the wild-type p53 activity, the hotspot p53 mutants also acquire new oncogenic functions, so-called ‘gain-of-functions’ (GOF). Because the GOF of mutant p53 is highly associated with late-stage malignance and drug resistance, these p53 mutants have become hot targets for developing novel cancer therapies. In this essay, we review some recent progresses in better understanding of the role of mutant p53 GOF in chemoresistance and the underlying mechanisms, and discuss the pros and cons of targeting mutant p53 for the development of anti-cancer therapies.