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Drugging p53 in cancer: one protein, many targets
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“Given the pathogenic role of TP53 mutations in cancer pathogenesis and drug resistance, TP53 mutations are attractive therapeutic targets 35, 36.”
From Combined Point Mutation in a Single Allele of the TP53 Gene Potentiates the Oncogenic and Transcriptional Properties of TP53 in Lung Cancer (2026) · cites this paper as [35]
In the citing paper
“Therefore, p53 is widely regarded as “undruggable”.12”
From p53: from understanding its structure to advances in therapeutic targeting (2026) · cites this paper as [12]
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“Recently, a phase II trial utilizing a combination of APR-246 and AZA as post-transplant maintenance treatments evaluated their efficacy in MDS and AML patients with mutant p53. The relapse-free survival (RFS) 1 year after transplantation and median overall survival (OS) in this study were 58% and 19.3 months, respectively.”
From p53: from understanding its structure to advances in therapeutic targeting (2026) · cites this paper as [12]
In the citing paper
“Specifically, the p53 R175H mutation decreases the binding affinity of the DBD and Zn2+ and promotes incorrect folding and inactivation of the p53 protein.12”
From p53: from understanding its structure to advances in therapeutic targeting (2026) · cites this paper as [12]
In the citing paper
“Currently, there are two approaches to rescue truncated p53.557 One is to restore production of full-length p53 protein by drug-induced read-through of the premature termination codon.”
From Targeting p53 pathways: mechanisms, structures, and advances in therapy (2023) · cites this paper as [557]
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Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage
Komor, A. C., Kim, Y. B., Packer, M. S., Zuris, J. A., & Liu, D. R. (2016) · Nature · doi:10.1038/nature17946 · Cited by 5,437
In Vivo Activation of the p53 Pathway by Small-Molecule Antagonists of MDM2
Vassilev, L. T., Vu, B. T., Graves, B., Carvajal, D., Podlaski, F., Filipovic, Z., Kong, N., Kammlott, U., Lukacs, C., Klein, C., et al. (2004) · Science · doi:10.1126/science.1092472 · Cited by 4,661
Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas
Xue, W., Zender, L., Miething, C., Dickins, R. A., Hernando, E., Krizhanovsky, V., Cordon-Cardo, C., & Lowe, S. W. (2007) · Nature · doi:10.1038/nature05529 · Cited by 2,473
TP53 mutations in human cancers: origins, consequences, and clinical use.
Olivier, M., Hollstein, M., & Hainaut, P. (2010) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a001008 · Cited by 2,199
Amplification of a gene encoding a p53-associated protein in human sarcomas
Oliner, J. D., Kinzler, K. W., Meltzer, P. S., George, D. L., & Vogelstein, B. (1992) · Nature · doi:10.1038/358080a0 · Cited by 1,949
Restoration of p53 function leads to tumour regression in vivo
Ventura, A., Kirsch, D. G., McLaughlin, M. E., Tuveson, D. A., Grimm, J., Lintault, L., Newman, J., Reczek, E. E., Weissleder, R., & Jacks, T. (2007) · Nature · doi:10.1038/nature05541 · Cited by 1,820
KRAS G12C Inhibition with Sotorasib in Advanced Solid Tumors
Hong, D. S., Fakih, M. G., Strickler, J. H., Desai, J., Durm, G. A., Shapiro, G. I., Falchook, G. S., Price, T. J., Sacher, A., Denlinger, C. S., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa1917239 · Cited by 1,733
Fridman, J. S., & Lowe, S. W. (2003) · Oncogene · doi:10.1038/sj.onc.1207116 · Cited by 1,401
MDM2, MDMX and p53 in oncogenesis and cancer therapy
Wade, M., Li, Y.-C., & Wahl, G. M. (2013) · Nature Reviews Cancer · doi:10.1038/nrc3430 · Cited by 1,279
CRISPR–Cas9 genome editing induces a p53-mediated DNA damage response
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Metadata
- Authors
- Hassin, O., & Oren, M.
- Venue
- Nature Reviews Drug Discovery
- Published
- 2022-10-10
- Volume
- 22
- Issue
- 2
- Pages
- 127-144
- ISSN
- 1474-1776
- 1474-1784
- Cited by
- 697
- References
- 54
- Language
- en
- Licence
- www.springernature.com/gp/researchers/text-and-data-mining (tdm)
- www.springernature.com/gp/researchers/text-and-data-mining (vor)
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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