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Cited by 82Cancer-related Molecular PathwaysPI3K/AKT/mTOR signaling in cancerHeat shock proteins research

Pharmacological reactivation of p53 as a strategy to treat cancer

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Zawacka‐Pankau, J., Selivanova, G.·2015·Journal of Internal Medicine
DOI 10.1111/joim.12336
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Abstract

It has been confirmed through studies using the technique of unbiased sequencing that the TP53 tumour suppressor is the most frequently inactivated gene in cancer. This finding, together with results from earlier studies, provides compelling evidence for the idea that p53 ablation is required for the development and maintenance of tumours. Genetic reconstitution of the function of p53 leads to the suppression of established tumours as shown in mouse models. This strongly supports the notion that p53 reactivation by small molecules could provide an efficient strategy to treat cancer. In this review, we summarize recent advances in the development of small molecules that restore the function of mutant p53 by different mechanisms, including stabilization of its folding by A pr‐246, which is currently being tested in a Phase II clinical trial. We discuss several classes of compounds that reactivate wild‐type p53, such as Mdm2 inhibitors, which are currently undergoing clinical testing, MdmX inhibitors and molecules targeting factors upstream of Mdm2/X or p53 itself. Finally, we consider the clinical applications of compounds targeting p53 and the p53 pathway.

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  • Several small molecules have been identified that inactivate mutant p53 or restore WT p53 response in mutant p53 protein including PRIMA-1, MIRA-1, Elipticin, CDB3, WR1065, NSC319726, p53R3 and CP-31398, although their mechanisms of action in many cases remain to be clarified.

    “Over the past decade, several small molecules have been identified that inactivate mutant p53 or restore WT p53 response in mutant p53 protein including PRIMA-1, MIRA-1, Elipticin, CDB3, WR1065, NSC319726, p53R3 and CP-31398, although their mechanisms of action in many cases remain to be clarified [9].”

    From Ligand dependent restoration of human TLR3 signaling and death in p53 mutant cells (2016) · cites this paper as [9]

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Cited by

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Authors
Zawacka‐Pankau, J., & Selivanova, G.
Affiliations
Karolinska Institutet (SE)
Corresponding author
  • Zawacka‐Pankau, J.
  • Selivanova, G.
ORCID
Venue
Journal of Internal Medicine
Publisher
Wiley
Published
2015-01-26
Volume
277
Issue
2
Pages
248-259
ISSN
  • 0954-6820 (ISSN-L)
  • 1365-2796
DOI
10.1111/joim.12336
OpenAlex
W2066511043
Cited by
82
References
16
Citations by year
2026: 3 · 2025: 4 · 2024: 4 · 2023: 2 · 2022: 9 · 2021: 4 · 2020: 4 · 2019: 10 · 2018: 9 · 2017: 10 · 2016: 12 · 2015: 9 · 2014: 1
FWCI
1.21
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Journal of Internal Medicine (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Swedish Research Council
  • Swedish Cancer Society
  • Karolinska Institutet
  • Knut and Alice Wallenberg Foundation
  • Polish Ministry of Science
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 › Heat shock proteins research
Keywords
p53 reactivation, TP53, mutant p53, small molecule p53 activators, APR-246, MDM2 inhibitors, p53 stabilization, p53 pathway, tumor suppressor inactivation, cancer therapy
MeSH terms
Alleles, Animals, Antineoplastic Agents, Humans, Neoplasms, Phenotype, Signal Transduction, Tumor Suppressor Protein p53, Treatment Outcome, Clinical Trials, Phase II as Topic, Evidence-Based Medicine, Mutation, Missense, Mice, Proto-Oncogene Proteins c-mdm2, Molecular Targeted Therapy

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