Mutant p53 in cancer: from molecular mechanism to therapeutic modulation

TP53 , a crucial tumor suppressor gene, is the most commonly mutated gene in human cancers. Aside from losing its tumor suppressor function, mutant p53 (mutp53) often acquires inherent, novel oncogenic functions, which is termed “gain-of-function”. Emerging evidence suggests that mutp53 is highly as...

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Published in:Cell death & disease 2022-11, Vol.13 (11), p.974-14, Article 974
Main Authors: Chen, Xiaohua, Zhang, Taotao, Su, Wei, Dou, Zhihui, Zhao, Dapeng, Jin, Xiaodong, Lei, Huiwen, Wang, Jing, Xie, Xiaodong, Cheng, Bo, Li, Qiang, Zhang, Hong, Di, Cuixia
Format: Article
Language:English
Subjects:
631/67/395
692/699/67
Antibodies
Biochemistry
Biomedical and Life Sciences
Cancer
Carcinogenesis - genetics
Cell Biology
Cell Culture
Chemotherapy
Ferroptosis
Genes, p53
Genomic instability
Humans
Immunology
Life Sciences
Malignancy
Microenvironments
Mutants
Mutation - genetics
Neoplasms - drug therapy
Neoplasms - therapy
p53 Protein
Radiation therapy
Review
Review Article
Tumor Microenvironment
Tumor suppressor genes
Tumor Suppressor Protein p53 - genetics
Tumors
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Summary:TP53 , a crucial tumor suppressor gene, is the most commonly mutated gene in human cancers. Aside from losing its tumor suppressor function, mutant p53 (mutp53) often acquires inherent, novel oncogenic functions, which is termed “gain-of-function”. Emerging evidence suggests that mutp53 is highly associated with advanced malignancies and poor prognosis, which makes it a target for development of novel cancer therapies. Herein, we provide a summary of our knowledge of the mutp53 types and mutp53 spectrum in cancers. The mechanisms of mutp53 accumulation and gain-of-function are also summarized. Furthermore, we discuss the gain-of-function of mutp53 in cancers: genetic instability, ferroptosis, microenvironment, and stemness. Importantly, the role of mutp53 in the clinic is also discussed, particularly with regard to chemotherapy and radiotherapy. Last, emphasis is given to emerging strategies on how to target mutp53 for tumor therapy. Thus, this review will contribute to better understanding of the significance of mutp53 as a target for therapeutic strategies.
ISSN:2041-4889
2041-4889
DOI:10.1038/s41419-022-05408-1