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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1 retracted

RETRACTED: Gentamicin B1 is a minor gentamicin component with major nonsense mutation suppression activity
Baradaran‐Heravi, A., Niesser, J., Balgi, A. D., Choi, K., Zimmerman, C., South, A. P., Anderson, H. J., Strynadka, N. C. J., Bally, M. B., & Roberge, M. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1620982114 · Cited by 52
Retracted
The Protein Data Bank
Berman, H. M. (2000) · Nucleic Acids Research · doi:10.1093/nar/28.1.235 · Cited by 40,196
The cBio Cancer Genomics Portal: An Open Platform for Exploring Multidimensional Cancer Genomics Data
Cerami, E., Gao, J., Dogrusoz, U., Gross, B. E., Sumer, S. O., Aksoy, B. A., Jacobsen, A., Byrne, C. J., Heuer, M. L., Larsson, E., et al. (2012) · Cancer Discovery · doi:10.1158/2159-8290.cd-12-0095 · Cited by 17,455
p53 Mutations in Human Cancers
Hollstein, M., Sidransky, D., Vogelstein, B., & Harris, C. C. (1991) · Science · doi:10.1126/science.1905840 · Cited by 8,018
Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours
Donehower, L. A., Harvey, M., Slagle, B. L., McArthur, M. J., Montgomery, C. A., Butel, J. S., & Bradley, A. (1992) · Nature · doi:10.1038/356215a0 · Cited by 4,649
Mutational landscape and significance across 12 major cancer types
Kandoth, C., McLellan, M. D., Vandin, F., Ye, K., Niu, B., Lu, C., Xie, M., Zhang, Q., McMichael, J. F., Wyczalkowski, M. A., et al. (2013) · Nature · doi:10.1038/nature12634 · Cited by 4,419
Germ Line p53 Mutations in a Familial Syndrome of Breast Cancer, Sarcomas, and Other Neoplasms
Malkin, D., Li, F. P., Strong, L. C., Fraumeni, J. F., Nelson, C. E., Kim, D. H., Kassel, J., Gryka, M. A., Bischoff, F. Z., Tainsky, M. A., et al. (1990) · Science · doi:10.1126/science.1978757 · Cited by 3,765
Update on Key Emerging Challenges in Cystic Fibrosis
Jennings, M. T., Riekert, K. A., & Boyle, M. (2014) · Medical Principles and Practice · doi:10.1159/000357646 · Cited by 3,671
Modulation of oxidative stress as an anticancer strategy
Gorrini, C., Harris, I. S., & Mak, T. W. (2013) · Nature Reviews Drug Discovery · doi:10.1038/nrd4002 · Cited by 3,579
Ferroptosis as a p53-mediated activity during tumour suppression
Jiang, L., Kon, N., Li, T., Wang, S.-J., Su, T., Hibshoosh, H., Baer, R., & Gu, W. (2015) · Nature · doi:10.1038/nature14344 · Cited by 3,398

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Shi, H., Calvez, F. L., Olivier, M. & Hainaut, P. in 25 years of p53 research ( eds Hainaut, P., Wiman, K. G. ) 293–319 (Springer, 2005).

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Background
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BackgroundSelf-citation
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Background
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BackgroundMethod
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Retracted
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Background
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BackgroundMethod
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Background
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Background
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Wang, M., Yang, Z., Song, Y., Wei, P., Ishimwe, N., Wang, L., Zhang, H., Jing, M., Gao, M., Wen, L., et al. (2022) · Acta Biomaterialia · doi:10.1016/j.actbio.2022.07.057 · Cited by 13
Drug Design of “Undruggable” Targets
Wang, J., Li, S., & Li, H. (2019) · Chinese Journal of Chemistry · doi:10.1002/cjoc.201800552 · Cited by 13
A TP53-associated immune prognostic signature for the prediction of the overall survival and therapeutic responses in pancreatic cancer
Liu, Y., Department of Colorectal and Anal Surgery, T. F. H. O. J. U., Cheng, L., Song, X., Li, C., Zhang, J., Wang, L., Department of Orthopedics, T. F. H. O. J. U., & Department of Hepatobiliary and Pancreatic Surgery, T. F. H. O. J. U. (2022) · Mathematical Biosciences and Engineering · doi:10.3934/mbe.2022010 · Cited by 14
Multi-Omic Analysis of Two Common P53 Mutations: Proteins Regulated by Mutated P53 as Potential Targets for Immunotherapy
Vadakekolathu, J. N., Boocock, D. J., Pandey, K., Guinn, B., Legrand, A., Miles, A. K., Coveney, C., Ayala, R., Purcell, A. W., & McArdle, S. (2022) · Cancers · doi:10.3390/cancers14163975 · Cited by 13
“Currently, the most promising TP53-targetting therapies involve blocking the degradation of the wild type protein using small molecules and stapled peptides [37], the reactivation of mutant forms of TP53 with wild type properties [36] and, increasingly, the development of mutant p53-specific bispecific antibodies, whi…”
Background
Hippo pathway in intestinal diseases: focusing on ferroptosis
Deng, H., Jia, Q., Ming, X., Sun, Y., Lu, Y., Liu, L., & Zhou, J. F. (2023) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2023.1291686 · Cited by 12
Pan-cancer analysis of RNA 5-methylcytosine reader (ALYREF)
Ye, X., Tuo, Z., Chen, K., Wu, R., Wang, J., Yu, Q., Ye, L., MIYAMOTO, A., Yoo, K. H., Zhang, C., et al. (2024) · Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics · doi:10.32604/or.2024.045050 · Cited by 13
“However, TP53 mutations often lead to p53 inactivation, enabling tumor cells to evade death and grow rapidly [89,92,93].”
Background
Ferroptosis in cancer (Review)
Zeng, L., Liu, X., Geng, C., Gao, X., & Liu, L. (2024) · Oncology Letters · doi:10.3892/ol.2024.14437 · Cited by 13
“It has been demonstrated that P53 deletions and mutations are linked to ~50% of all human malignancies (55).”
Background
GC–MS analysis, molecular docking, and apoptotic-based cytotoxic effect of Caladium lindenii Madison extracts toward the HeLa cervical cancer cell line
Kalsoom, A., Altaf, A., Sarwar, M., Maqbool, T., Ashraf, M. A. B., Sattar, H., Shabbir, G., Ali, Q., & Javed, M. A. (2024) · Scientific Reports · doi:10.1038/s41598-024-69582-2 · Cited by 12
“The p53 expression and function can be associated with the suppressive effect of many medicinal plants on cell growth and proliferation of cancer cells 63 .”
Background
CDKN1A promotes Cis-induced AKI by inducing cytoplasmic ROS production and ferroptosis
Gao, Q., Chen, J.-M., Li, C.-S.-Z., Zhan, J.-Y., Yin, X.-D., Li, B.-S., Dong, H., Luo, L., & Li, Z. (2024) · Food and Chemical Toxicology · doi:10.1016/j.fct.2024.115003 · Cited by 12
Unveiling the mechanism of sericin and hydroxychloroquine in suppressing lung oxidative impairment and early carcinogenesis in diethylnitrosamine-induced mice by modulating PI3K/Akt/Nrf2/NF-κB signaling pathway
El‐Samad, L. M., Maklad, A. M., Elkady, A. I., & Hassan, M. A. (2024) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2024.117730 · Cited by 12
Toward urinary cell-free DNA-based treatment of urothelial carcinoma: a narrative review
Hayashi, Y., & Fujita, K. (2021) · Translational Andrology and Urology · doi:10.21037/tau-20-1259 · Cited by 13
Establishment of a Novel Mouse Hepatocellular Carcinoma Model for Dynamic Monitoring of Tumor Development by Bioluminescence Imaging
Cao, X., Zhang, Y., Zhou, Q., Sujing, S., He, M., Wang, X., Ma, P., Yang, X., Lv, L., & Zhan, L. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.794101 · Cited by 12
“The tumor suppressor p53 plays a key role in inducing cellular senescence and death (25).”
Background
Dual-imaging magnetic nanocatalysis based on Fenton-like reaction for tumor therapy
Zhou, W., Tang, X., Huang, J., Wang, J., Zhao, J., Zhang, L., Wang, Z., Li, P., & Li, R. (2022) · Journal of Materials Chemistry B · doi:10.1039/d1tb02308j · Cited by 13
Design and synthesis of Nrf2-derived hydrocarbon stapled peptides for the disruption of protein-DNA-interactions
Wiedemann, B. M., Kamps, D., Depta, L., Weisner, J., Cvetreznik, J., Tomassi, S., Gentz, S., Hoffmann, J., Müller, M. P., Koch, O., et al. (2022) · PLoS ONE · doi:10.1371/journal.pone.0267651 · Cited by 12
Ampulla of Vater carcinoma: advancement in the relationships between histological subtypes, molecular features, and clinical outcomes
Liang, H., Zhu, Y. M., & Wu, Y. (2023) · Frontiers in Oncology · doi:10.3389/fonc.2023.1135324 · Cited by 12
“Tumor protein 53 gene (TP53) is a cellular stress sensor that is activated by conditions including DNA damage, improper mitogen stimulation, and oncogene activation (51).”
Background
MDM2 Implications for Potential Molecular Pathogenic Therapies of Soft-Tissue Tumors
Sun, S. Y. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12113638 · Cited by 12
Molecular Action of Herbal Antioxidants in Regulation of Cancer Growth: Scope for Novel Anticancer Drugs
Vinayak, M. (2018) · Nutrition and Cancer · doi:10.1080/01635581.2018.1539187 · Cited by 12
RITA downregulates Hedgehog-GLI in medulloblastoma and rhabdomyosarcoma via JNK-dependent but p53-independent mechanism
Azatyan, A., Gallo-Oller, G., Diao, Y., Selivanova, G., Johnsen, J. I., & Zaphiropoulos, P. G. (2018) · Cancer Letters · doi:10.1016/j.canlet.2018.11.005 · Cited by 12
Improvement in the Current Therapies for Hepatocellular Carcinoma Using a Systems Medicine Approach
Özcan, M., Altay, Ö., Lam, S. C. C., Türkez, H., Aksoy, Y., Nielsen, J., Uhlén, M., Borén, J., & Mardinoğlu, A. (2020) · Advanced Biosystems · doi:10.1002/adbi.202000030 · Cited by 12
Knockdown of ubiquitin-like modifier-activating enzyme 2 promotes apoptosis of clear cell renal cell carcinoma cells
Zhang, G., Zou, J., Shi, J., Qian, B., Qiu, K., Liu, Q., Xie, T., He, Z., Xu, H., Liao, Y., et al. (2021) · Cell Death and Disease · doi:10.1038/s41419-021-04347-7 · Cited by 12
“However, the function of p53 can be affected by some mutations [21].”
Background
The Regulatory Network and Role of the circRNA-miRNA-mRNA ceRNA Network in the Progression and the Immune Response of Wilms Tumor Based on RNA-Seq
Tian, X., Xiang, B., Zhang, Z., Li, Y., Shi, Q., Li, M., Li, Q., Yu, Y., Lu, P., Liu, F., et al. (2022) · Frontiers in Genetics · doi:10.3389/fgene.2022.849941 · Cited by 12
“Mutations in this gene are also potential prognostic and predictive markers, as well as targets for pharmacological intervention (Olivier et al., 2010; Bykov et al., 2018).”
Background
Induction of apoptosis and role of paclitaxel-loaded hyaluronic acid-crosslinked nanoparticles in the regulation of AKT and RhoA
Chaudhry, G.-E.-S., Akim, A. M., Zafar, M., Abdullah, M., Sung, Y. Y., & Muhammad, T. S. T. (2020) · Journal of Advanced Pharmaceutical Technology amp Research · doi:10.4103/japtr.japtr_26_20 · Cited by 12
“However, this may suggest the presence of a p53 mutant, as the majority of colorectal cancer cell lines are p53 mutated, amino acids 273 Arginine mutates into Histidine results in dysregulation in cell-cycle checkpoints.[16-18]”
Background
TP53-mutated MDS and AML: immune dysregulation, tumor microenvironment, and emerging therapeutic strategies
Albakri, M. M. (2025) · Frontiers in Oncology · doi:10.3389/fonc.2025.1655486 · Cited by 13
Bioinformatics and experimental validation of an AURKA/TPX2 axis as a potential target in esophageal squamous cell carcinoma
Du, R., Li, K., Zhou, Z., Huang, Y., Guo, K., Zhang, H., Chen, Z., Zhao, X., Han, L. B., & Bian, H. (2023) · Oncology Reports · doi:10.3892/or.2023.8553 · Cited by 11
Accurate interpretation of p53 immunohistochemical patterns is a surrogate biomarker for TP53 alterations in large B-cell lymphoma
Li, X., Luo, D., Zhang, L., Li, Q., Fan, J., Zhang, J., Huang, B., Yang, M., Nie, X., Chang, X., et al. (2023) · BMC Cancer · doi:10.1186/s12885-023-11513-x · Cited by 13
“%) of TP53 mutations in cancers are missense mutations in the DNA-binding core domain (codons 100-300) [30].”
Background
Recent Progress on Tumor Microenvironment‐Activated NIR‐II Phototheranostic Agents with Simultaneous Activation for Diagnosis and Treatment
Xiao, H., Wu, G., Tan, S., Tan, X., & Yang, Q. (2024) · Chemistry - An Asian Journal · doi:10.1002/asia.202301036 · Cited by 11
NIR Emissive Functional Nanoparticles Promote Precise Pancreatic Cancer Therapy by Co‐Targeting Mutant p53 and Oncogenic KRAS
Qian, J., Yang, Z., Zhang, W., Ye, Y., Song, Y., Ye, Y., Zhou, Y., Zheng, Q.-Q., Huang, X., Du, S., et al. (2024) · Advanced Functional Materials · doi:10.1002/adfm.202312610 · Cited by 11
Precision Medicine Approaches in Acute Myeloid Leukemia with Adverse Genetics
Santoro, N., Salutari, P., Ianni, M. D., & Marra, A. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25084259 · Cited by 10
“APR-246/eprenetapopt is a small molecule that targets TP53-mutated cancers [98,99], which has shown promising results against TP53 -mutated MDS and AML [100–102].”
Background
Science in Focus: Genomic Instability and its Implications for Clinical Cancer Care
Ahmad, S. S., Ahmed, K., & Venkitaraman, A. R. (2018) · Clinical Oncology · doi:10.1016/j.clon.2018.09.001 · Cited by 11
Knockdown of TXNDC9 induces apoptosis and autophagy in glioma and mediates cell differentiation by p53 activation
Zheng, T., Chen, K., Zhang, X. Z., Feng, H., Shi, Y., Liu, L., Zhang, J., & Chen, Y. (2020) · Aging · doi:10.18632/aging.103915 · Cited by 11
New Treatment Options for Older Patients with Acute Myeloid Leukemia
Saxena, K., & Konopleva, M. Y. (2021) · Current Treatment Options in Oncology · doi:10.1007/s11864-021-00841-4 · Cited by 11
Innovative dual system approach for selective eradication of cancer cells using viral-based delivery of natural bacterial toxin–antitoxin system
Shapira, S., Boustanai, I., Kazanov, D., Shimon, M. B., Fokra, A., & Arber, N. (2021) · Oncogene · doi:10.1038/s41388-021-01792-8 · Cited by 11
“Upon activation, p53 and its downstream target genes induce cell cycle arrest, allowing either repair and cell survival or, in case of irreversible damage, activation of senescence and apoptotic pathways [1, 13, 14].”
Background
Investigation on the Potential Correlation Between TP53 and Esophageal Cancer
Yao, L., Zhong, X., Huang, G., Ma, Q., Xu, L., Xiao, H., & Guo, X. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.730337 · Cited by 11
“TP53 is a tumor suppressor gene associated with neoplastic disease (Bykov et al., 2018), while TP53 gene mutations occur in about half of human cancers (Kandoth et al., 2013).”
Background
Colletofragarone A2 and Colletoins A–C from a Fungus Colletotrichum sp. Decrease Mutant p53 Levels in Cells
Sadahiro, Y., Hitora, Y., & Tsukamoto, S. (2021) · Journal of Natural Products · doi:10.1021/acs.jnatprod.1c00913 · Cited by 11
Chromosome‐level Asian elephant genome assembly and comparative genomics of long‐lived mammals reveal the common substitutions for cancer resistance
Li, X., Wang, P., Pan, Q., Liu, G., Liu, W., Omotoso, O., Du, J., Li, Z., Yu, Y., Huang, Y., et al. (2023) · Aging Cell · doi:10.1111/acel.13917 · Cited by 10
Association of mRNA expression of TP53 and the TP53 codon 72 Arg/Pro gene polymorphism with colorectal cancer risk in Asian population: a bioinformatics analysis and meta-analysis
Dong, Z., Zheng, L., Liu, W., & Wang, C. (2018) · Cancer Management and Research · doi:10.2147/cmar.s164892 · Cited by 11
“39 Loes et al 40 reported the mutations of KRAS and BRAF to be a strong prognostic parameter in patients with metastatic colorectal cancer after treatment with partial liver resections, but not TP53.”
Re-expression of DIRAS3 and p53 induces apoptosis and impaired autophagy in head and neck squamous cell carcinoma
Liu, Z., Hurst, D. R., Qu, X., Lu, L.-G., Wu, C., Li, Y., & Li, Y. (2020) · Military Medical Research · doi:10.1186/s40779-020-00275-3 · Cited by 11

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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