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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Veröffentlicht in:	Cell death & disease Jg. 13; H. 11; S. 974 - 14
Hauptverfasser:	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:	Journal Article
Sprache:	Englisch
Veröffentlicht:	London Nature Publishing Group UK 18.11.2022 Springer Nature B.V Nature Publishing Group
Schlagworte:	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
Online-Zugang:	Volltext
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Abstract	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.
AbstractList	Abstract 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. 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. 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.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. 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.
ArticleNumber	974
Author	Lei, Huiwen Dou, Zhihui Zhang, Hong Su, Wei Wang, Jing Chen, Xiaohua Li, Qiang Jin, Xiaodong Zhang, Taotao Zhao, Dapeng Cheng, Bo Di, Cuixia Xie, Xiaodong
Author_xml	– sequence: 1 givenname: Xiaohua surname: Chen fullname: Chen, Xiaohua organization: Bio-Medical Research Center, Institute of Modern Physics, Chinese Academy of Sciences, Advanced Energy Science and Technology Guangdong Laboratory, Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, College of Life Sciences, University of Chinese Academy of Sciences, School of Nuclear Science and Technology, University of Chinese Academy of Sciences – sequence: 2 givenname: Taotao surname: Zhang fullname: Zhang, Taotao organization: Bio-Medical Research Center, Institute of Modern Physics, Chinese Academy of Sciences, Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, College of Life Sciences, University of Chinese Academy of Sciences, School of Nuclear Science and Technology, University of Chinese Academy of Sciences – sequence: 3 givenname: Wei surname: Su fullname: Su, Wei organization: Bio-Medical Research Center, Institute of Modern Physics, Chinese Academy of Sciences, Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, College of Life Sciences, University of Chinese Academy of Sciences, School of Nuclear Science and Technology, University of Chinese Academy of Sciences – sequence: 4 givenname: Zhihui surname: Dou fullname: Dou, Zhihui organization: Bio-Medical Research Center, Institute of Modern Physics, Chinese Academy of Sciences, Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, College of Life Sciences, University of Chinese Academy of Sciences, School of Nuclear Science and Technology, University of Chinese Academy of Sciences – sequence: 5 givenname: Dapeng surname: Zhao fullname: Zhao, Dapeng organization: Bio-Medical Research Center, Institute of Modern Physics, Chinese Academy of Sciences, Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, College of Life Sciences, University of Chinese Academy of Sciences, School of Nuclear Science and Technology, University of Chinese Academy of Sciences – sequence: 6 givenname: Xiaodong surname: Jin fullname: Jin, Xiaodong organization: Bio-Medical Research Center, Institute of Modern Physics, Chinese Academy of Sciences, Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences – sequence: 7 givenname: Huiwen surname: Lei fullname: Lei, Huiwen organization: Bio-Medical Research Center, Institute of Modern Physics, Chinese Academy of Sciences, Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, College of Life Sciences, University of Chinese Academy of Sciences, School of Nuclear Science and Technology, University of Chinese Academy of Sciences – sequence: 8 givenname: Jing surname: Wang fullname: Wang, Jing organization: School of Basic Medical Sciences, Lanzhou University – sequence: 9 givenname: Xiaodong surname: Xie fullname: Xie, Xiaodong organization: School of Basic Medical Sciences, Lanzhou University – sequence: 10 givenname: Bo surname: Cheng fullname: Cheng, Bo organization: School of Life Sciences, Lanzhou University – sequence: 11 givenname: Qiang orcidid: 0000-0003-0096-7679 surname: Li fullname: Li, Qiang email: liqiang@impcas.ac.cn organization: Bio-Medical Research Center, Institute of Modern Physics, Chinese Academy of Sciences, Advanced Energy Science and Technology Guangdong Laboratory, Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, College of Life Sciences, University of Chinese Academy of Sciences, School of Nuclear Science and Technology, University of Chinese Academy of Sciences, Lanhai Neclear Medical Research Center – sequence: 12 givenname: Hong surname: Zhang fullname: Zhang, Hong email: zhang.h@impcas.ac.cn organization: Bio-Medical Research Center, Institute of Modern Physics, Chinese Academy of Sciences, Advanced Energy Science and Technology Guangdong Laboratory, Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, College of Life Sciences, University of Chinese Academy of Sciences, School of Nuclear Science and Technology, University of Chinese Academy of Sciences – sequence: 13 givenname: Cuixia orcidid: 0000-0002-8155-9521 surname: Di fullname: Di, Cuixia email: dicx@impcas.ac.cn organization: Bio-Medical Research Center, Institute of Modern Physics, Chinese Academy of Sciences, Advanced Energy Science and Technology Guangdong Laboratory, Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, College of Life Sciences, University of Chinese Academy of Sciences, School of Nuclear Science and Technology, University of Chinese Academy of Sciences, Lanhai Neclear Medical Research Center
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Snippet	TP53 , a crucial tumor suppressor gene, is the most commonly mutated gene in human cancers. Aside from losing its tumor suppressor function, mutant p53... 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)... Abstract TP53, a crucial tumor suppressor gene, is the most commonly mutated gene in human cancers. Aside from losing its tumor suppressor function, mutant p53...
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SubjectTerms	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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Title	Mutant p53 in cancer: from molecular mechanism to therapeutic modulation
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