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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Additional file 2 of A novel predictive model of microvascular invasion in hepatocellular carcinoma based on differential protein expression
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Additional file 1 of PCNA-associated factor (KIAA0101/PCLAF) overexpression and gene copy number alterations in hepatocellular carcinoma tissues
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Additional file 2 of Mutant p53-ENTPD5 control of the calnexin/calreticulin cycle: a druggable target for inhibiting integrin-α5-driven metastasis
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Additional file 6 of Mutant p53-ENTPD5 control of the calnexin/calreticulin cycle: a druggable target for inhibiting integrin-α5-driven metastasis
Pavlakis, E., Neumann, M., Merle, N., Wieboldt, R., Wanzel, M., Ponath, V., von Strandmann, E. P., Elmshäuser, S., & Stiewe, T. (2023) · Figshare · doi:10.6084/m9.figshare.23930434
Additional file 2 of Identification and validation of a novel prognosis model based on m5C-related long non-coding RNAs in colorectal cancer
Di, Z., Xu, G., Ding, Z., Li, C., Song, J., Huang, G., Zheng, J., Zhang, X., & Xiong, B. (2023) · Figshare · doi:10.6084/m9.figshare.24091727
Additional file 4 of Mutant p53-ENTPD5 control of the calnexin/calreticulin cycle: a druggable target for inhibiting integrin-α5-driven metastasis
Pavlakis, E., Neumann, M., Merle, N., Wieboldt, R., Wanzel, M., Ponath, V., von Strandmann, E. P., Elmshäuser, S., & Stiewe, T. (2023) · Figshare · doi:10.6084/m9.figshare.23930428
Additional file 2 of High expression of ABCF1 is an independent predictor of poor prognosis in bladder cancer
Fan, J., Ding, Y., Huang, H., Xiong, S., He, L., & Guo, J. (2024) · Figshare · doi:10.6084/m9.figshare.26575730
Additional file 1 of Characterization of TGFβ-associated molecular features and drug responses in gastrointestinal adenocarcinoma
Zhang, Q., Liu, F., Qin, L., Liao, Z., Song, J., Liang, H., Chen, X., Zhang, Z., & Zhang, B. (2021) · Figshare · doi:10.6084/m9.figshare.14955954
Additional file 1 of Identification and validation of a novel prognosis model based on m5C-related long non-coding RNAs in colorectal cancer
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Additional file 5 of High expression of ABCF1 is an independent predictor of poor prognosis in bladder cancer
Fan, J., Ding, Y., Huang, H., Xiong, S., He, L., & Guo, J. (2024) · Figshare · doi:10.6084/m9.figshare.26575739
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Additional file 6 of High expression of ABCF1 is an independent predictor of poor prognosis in bladder cancer
Fan, J., Ding, Y., Huang, H., Xiong, S., He, L., & Guo, J. (2024) · Figshare · doi:10.6084/m9.figshare.26575742
Additional file 2 of PCNA-associated factor (KIAA0101/PCLAF) overexpression and gene copy number alterations in hepatocellular carcinoma tissues
Tantiwetrueangdet, A., Panvichian, R., Sornmayura, P., Leelaudomlipi, S., & Macoska, J. A. (2021) · Figshare · doi:10.6084/m9.figshare.14253870
Additional file 5 of PCNA-associated factor (KIAA0101/PCLAF) overexpression and gene copy number alterations in hepatocellular carcinoma tissues
Tantiwetrueangdet, A., Panvichian, R., Sornmayura, P., Leelaudomlipi, S., & Macoska, J. A. (2021) · Figshare · doi:10.6084/m9.figshare.14253879
Additional file 1 of High expression of ABCF1 is an independent predictor of poor prognosis in bladder cancer
Fan, J., Ding, Y., Huang, H., Xiong, S., He, L., & Guo, J. (2024) · Figshare · doi:10.6084/m9.figshare.26575727
Additional file 1 of A novel predictive model of microvascular invasion in hepatocellular carcinoma based on differential protein expression
Wang, Z., Cao, L., Wang, J., Wang, H., Ma, T., Yin, Z., Cai, W., Liu, L., Liu, T., Ma, H., et al. (2023) · Figshare · doi:10.6084/m9.figshare.22617443
Additional file 2 of TP53 missense mutation reveals gain-of-function properties in small-sized KRAS transformed pancreatic ductal adenocarcinoma
Zhou, Y., Jin, J., Ji, Y., Zhang, J., Fu, N., Chen, M., Wang, J., Qin, K., Jiang, Y., 程东峰, et al. (2024) · Figshare · doi:10.6084/m9.figshare.24709141
Additional file 1 of Mutant p53-ENTPD5 control of the calnexin/calreticulin cycle: a druggable target for inhibiting integrin-α5-driven metastasis
Pavlakis, E., Neumann, M., Merle, N., Wieboldt, R., Wanzel, M., Ponath, V., von Strandmann, E. P., Elmshäuser, S., & Stiewe, T. (2023) · Figshare · doi:10.6084/m9.figshare.23930419
Additional file 6 of PCNA-associated factor (KIAA0101/PCLAF) overexpression and gene copy number alterations in hepatocellular carcinoma tissues
Tantiwetrueangdet, A., Panvichian, R., Sornmayura, P., Leelaudomlipi, S., & Macoska, J. A. (2021) · Figshare · doi:10.6084/m9.figshare.14253882
Additional file 3 of PCNA-associated factor (KIAA0101/PCLAF) overexpression and gene copy number alterations in hepatocellular carcinoma tissues
Tantiwetrueangdet, A., Panvichian, R., Sornmayura, P., Leelaudomlipi, S., & Macoska, J. A. (2021) · Figshare · doi:10.6084/m9.figshare.14253873
Additional file 3 of Mutant p53-ENTPD5 control of the calnexin/calreticulin cycle: a druggable target for inhibiting integrin-α5-driven metastasis
Pavlakis, E., Neumann, M., Merle, N., Wieboldt, R., Wanzel, M., Ponath, V., von Strandmann, E. P., Elmshäuser, S., & Stiewe, T. (2023) · Figshare · doi:10.6084/m9.figshare.23930425
Additional file 3 of TP53 missense mutation reveals gain-of-function properties in small-sized KRAS transformed pancreatic ductal adenocarcinoma
Zhou, Y., Jin, J., Ji, Y., Zhang, J., Fu, N., Chen, M., Wang, J., Qin, K., Jiang, Y., 程东峰, et al. (2024) · Figshare · doi:10.6084/m9.figshare.26648016
Additional file 7 of Mutant p53-ENTPD5 control of the calnexin/calreticulin cycle: a druggable target for inhibiting integrin-α5-driven metastasis
Pavlakis, E., Neumann, M., Merle, N., Wieboldt, R., Wanzel, M., Ponath, V., von Strandmann, E. P., Elmshäuser, S., & Stiewe, T. (2023) · Figshare · doi:10.6084/m9.figshare.23930437
Additional file 3 of A novel predictive model of microvascular invasion in hepatocellular carcinoma based on differential protein expression
Wang, Z., Cao, L., Wang, J., Wang, H., Ma, T., Yin, Z., Cai, W., Liu, L., Liu, T., Ma, H., et al. (2023) · Figshare · doi:10.6084/m9.figshare.22617449
Additional file 4 of High expression of ABCF1 is an independent predictor of poor prognosis in bladder cancer
Fan, J., Ding, Y., Huang, H., Xiong, S., He, L., & Guo, J. (2024) · Figshare · doi:10.6084/m9.figshare.26575736
Additional file 4 of TP53 missense mutation reveals gain-of-function properties in small-sized KRAS transformed pancreatic ductal adenocarcinoma
Zhou, Y., Jin, J., Ji, Y., Zhang, J., Fu, N., Chen, M., Wang, J., Qin, K., Jiang, Y., 程东峰, et al. (2024) · Figshare · doi:10.6084/m9.figshare.26648019
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Lella, S. D., Esposito, F., Matassa, D. S., & Avolio, R. (2026) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2026.189650
Functional restoration of conformational (R175H) and contact (R273H) mutant p53 by Bacillus-derived Hydroxymycotrienin A in non-small cell lung cancer: a computational approach
Rufus, A. C., Sidharth Kumar, N., Ramasamy, M., & Elangovan, E. (2026) · Frontiers in Bioinformatics · doi:10.3389/fbinf.2026.1875897
“( (Bykov et al., 2017).”
p53 hotspot mutants attenuate CTL-mediated tumor cell killing through a novel ALKBH5-YTHDF3-PD-L1 pathway
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Emerging mRNA-based nanomedicines for cancer immunotherapy
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“Genes associated with DNA repair, cell cycle arrest, apoptosis, and cellular senescence are among the key target genes for cancer prevention (Bykov et al. 2018; Gannon et al. 1990; Lu et al. 2023; Ting et al. 2019).”
Thiadiazolo‐Triazolo‐Pyrimidine Hybrids as Dual Aurora A/ERK Inhibitors: Design, Synthesis, and Apoptotic Activity
Mourad, M. A. E., Hofni, A., & Mourad, A. A. E. (2026) · Drug Development Research · doi:10.1002/ddr.70364
Revisiting tumor immunogenicity through the lens of mutant p53: Implications for cancer immunotherapy
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Molecular Glue and Phosphorylation-Dependent 14-3-3 Recruitment to p53 with an Engineered Interaction Cassette
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Mutant p53 gain-of-function and immune suppression: Mathematical modeling of STING–TBK1–IRF3 axis restoration for enhanced cancer therapy
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Covalent Targeting and Thermostabilization of Oncogenic R280K and R273H Mutants p53 by Small Molecule RVJB59
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Design of Multi-Epitope Cancer Vaccine Targeting p53 Tumor Antigen using Myotis lucifugus Sequencers: An Immunoinformatics Approach
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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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