Cited by 914Cancer-related Molecular PathwaysPI3K/AKT/mTOR signaling in cancerCancer Mechanisms and Therapy

Awakening guardian angels: drugging the p53 pathway

Brown, Christopher J., Lain, Sonia, Verma, Chandra S., Fersht, Alan R., Lane, David P.·2009·Nature Reviews Cancer

Abstract

Currently, around 11 million people are living with a tumour that contains an inactivating mutation of TP53 (the human gene that encodes p53) and another 11 million have tumours in which the p53 pathway is partially abrogated through the inactivation of other signalling or effector components. The p53 pathway is therefore a prime target for new cancer drug development, and several original approaches to drug discovery that could have wide applications to drug development are being used. In one approach, molecules that activate p53 by blocking protein-protein interactions with MDM2 are in early clinical development. Remarkable progress has also been made in the development of p53-binding molecules that can rescue the function of certain p53 mutants. Finally, cell-based assays are being used to discover compounds that exploit the p53 pathway by either seeking targets and compounds that show synthetic lethality with TP53 mutations or by looking for non-genotoxic activators of the p53 response.

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Crossref · 10.1038/nrc2763

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Authors
Brown, C. J., Lain, S., Verma, C. S., Fersht, A. R., & Lane, D. P.
Affiliations
  • Agency for Science, Technology and Research (SG)
  • Medical Research Council (GB)
Corresponding author
Lane, David P.
Venue
Nature Reviews Cancer
Published
2009-12
Volume
9
Issue
12
Pages
862-873
ISSN
  • 1474-175X (ISSN-L)
  • 1474-1768
OpenAlex
W2093775600
Cited by
881
References
149
Citations by year
2026: 5 · 2025: 24 · 2024: 21 · 2023: 64 · 2022: 27 · 2021: 32 · 2020: 37 · 2019: 49 · 2018: 42 · 2017: 59 · 2016: 58 · 2015: 76 · 2014: 91 · 2013: 74 · 2012: 82
FWCI
6.45
Type
journal article
Language
en
Open access
closed
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
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Cancer Mechanisms and Therapy
Keywords
p53 pathway, TP53 mutation, MDM2, p53 activation, mutant p53, synthetic lethality, cell-based assays, anticancer drug development, protein-protein interaction inhibitors
MeSH terms
Antineoplastic Agents, Humans, Mutation, Neoplasms, Drug Design, Signal Transduction, Genes, p53, Tumor Suppressor Protein p53, Drug Delivery Systems, Proto-Oncogene Proteins c-mdm2

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