Cited by 893Cancer-related Molecular PathwaysPI3K/AKT/mTOR signaling in cancerCell death mechanisms and regulation

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Targeting mutant p53 for efficient cancer therapy

Bykov, Vladimir J. N., Eriksson, Sofi E., Bianchi, Julie, Wiman, Klas G.·2018·Nature Reviews Cancer

DOI 10.1038/nrc.2017.109

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Abstract

The tumour suppressor gene TP53 is the most frequently mutated gene in cancer. Wild-type p53 can suppress tumour development by multiple pathways. However, mutation of TP53 and the resultant inactivation of p53 allow evasion of tumour cell death and rapid tumour progression. The high frequency of TP53 mutation in tumours has prompted efforts to restore normal function of mutant p53 and thereby trigger tumour cell death and tumour elimination. Small molecules that can reactivate missense-mutant p53 protein have been identified by different strategies, and two compounds are being tested in clinical trials. Novel approaches for targeting TP53 nonsense mutations are also underway. This Review discusses recent progress in pharmacological reactivation of mutant p53 and highlights problems and promises with these strategies.

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Authors: Bykov, V. J. N., Eriksson, S. E., Bianchi, J., & Wiman, K. G.
Affiliations: Karolinska Institutet (SE)
Corresponding author: Wiman, Klas G.
ORCID: Bykov, Vladimir J. N.
Eriksson, Sofi E.
Bianchi, Julie
Wiman, Klas G.
Venue: Nature Reviews Cancer
Publisher: Springer Science and Business Media LLC
Published: 2017-12-15
Volume: 18
Issue: 2
Pages: 89-102
ISSN: 1474-175X (ISSN-L)
1474-1768
DOI: 10.1038/nrc.2017.109
OpenAlex: W2772062014
Cited by: 889
References: 159
Citations by year: 2026: 43 · 2025: 70 · 2024: 100 · 2023: 132 · 2022: 126 · 2021: 150 · 2020: 129 · 2019: 88 · 2018: 49 · 2017: 1
FWCI: 7.67
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature reviews. Cancer (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
Keywords: TP53, mutant p53, p53 reactivation, missense mutations, nonsense mutation, tumor suppressor, cancer therapy, cancer cell death, clinical trials
MeSH terms: Animals, Antineoplastic Agents, Humans, Mutation, Neoplasms, Tumor Suppressor Protein p53, Cell Death, Mutant Proteins

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Targeting mutant p53 for efficient cancer therapy

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