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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Vydáno v:	Cell death & disease Ročník 13; číslo 11; s. 974 - 14
Hlavní autoři:	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
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	London Nature Publishing Group UK 18.11.2022 Springer Nature B.V Nature Publishing Group
Témata:	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
ISSN:	2041-4889, 2041-4889
On-line přístup:	Získat plný text
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Popis
Shrnutí:	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.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 ObjectType-Review-3 content type line 23
ISSN:	2041-4889 2041-4889
DOI:	10.1038/s41419-022-05408-1