The DOI matches its Crossref record; 87 of the 87 references it cites were found in a registry or an index.
Targeting Therapies for the p53 Protein in Cancer Treatments
Abstract
Half of all human cancers contain TP53 mutations, and in many other cancers, the function of the p53 protein is compromised. The diversity of these mutations and phenotypes presents a challenge to the development of drugs that target p53 mutant cancer cells. This review describes the rationale for many different approaches in the development of p53 targeted therapies: ( a) viruses and gene therapies, ( b) increased levels and activity of wild-type p53 proteins in cancer cells, ( c) p53 protein gain-of-function inhibitors, ( d) p53 protein loss-of-function structural correctors, ( e) mutant p53 protein synthetic lethal drugs interfering with the p53 pathway, and ( f) cellular immune responses to mutant p53 protein antigens. As these types of therapies are developed, tested, and evaluated, the best of them will have a significant impact upon cancer treatments and possibly prevention.
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In the citing paper
“Studies have shown that approximately half of all human cancers, including serous ovarian cancer, lung squamous cell cancer, lung small cell cancer, triple-negative breast cancer, and squamous esophageal cancer, have alterations in the p53 gene, resulting in a loss of p53 function or decreased p53 expression.”
From Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials (2023) · cites this paper as [206]
In the citing paper
“P53 can be categorized as mutant type or wild type, with mutant p53 promoting tumorigenesis and wild-type p53 having broad-spectrum tumor inhibition.”
From Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials (2023) · cites this paper as [206]
In the citing paper
“The p53 protein, a crucial tumor suppressor, plays a significant role in preventing cancer initiation and progression.206–208”
From Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials (2023) · cites this paper as [206]
Citations
Cites
Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a
Serrano, M., Lin, A. W., McCurrach, M. E., Beach, D., & Lowe, S. W. (1997) · Cell · doi:10.1016/s0092-8674(00)81902-9 · Cited by 5,218 · cited 2×
“Among the stresses that activate p53 and produce higher levels of transcription are DNA damage (Maltzman & Czyzyk 1984, Kastan et al. 1991), telomere erosion (Karlseder et al. 1999), metabolic alterations (Levine & Puzio-Kuter 2010), hypoxia (Sermeus & Michiels 2011), deficiencies in ribosomal biogenesis (Zhang & Lu 2…”
BackgroundIn 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
The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53
Scheffner, M., Werness, B. A., Huibregtse, J. M., Levine, A. J., & Howley, P. M. (1990) · Cell · doi:10.1016/0092-8674(90)90409-8 · Cited by 3,995
Self-citationFerroptosis 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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Self-citationAssociation of Human Papillomavirus Types 16 and 18 E6 Proteins with p53
Werness, B. A., Levine, A. J., & Howley, P. M. (1990) · Science · doi:10.1126/science.2157286 · Cited by 2,562
Self-citationCrystal Structure of a p53 Tumor Suppressor-DNA Complex: Understanding Tumorigenic Mutations
Cho, Y., Gorina, S., Jeffrey, P. D., & Pavletich, N. P. (1994) · Science · doi:10.1126/science.8023157 · Cited by 2,559 · cited 2×
“The X-ray (Cho et al. 1994) and nuclear magnetic resonance structures of the DBD ( Joerger et al. 2005) are known and show a compact structure, with several amino acids that make close contacts with DNA residues (248, 273, and 282) and a set of amino acids that are further away from the DNA and stabilize the overall s…”
BackgroundT antigen is bound to a host protein in SY40-transformed cells
Lane, D. P., & Crawford, L. V. (1979) · Nature · doi:10.1038/278261a0 · Cited by 2,456
Structure of the MDM2 Oncoprotein Bound to the p53 Tumor Suppressor Transactivation Domain
Kussie, P. H., Gorina, S., Marechal, V., Elenbaas, B., Moreau, J., Levine, A. J., & Pavletich, N. P. (1996) · Science · doi:10.1126/science.274.5289.948 · Cited by 2,206
Self-citationChromosome 17 Deletions and p53 Gene Mutations in Colorectal Carcinomas
Baker, S. J., Fearon, E. R., Nigro, J. M., Hamilton, S. R., Preisinger, A. C., Jessup, J. M., vanTuinen, P., Ledbetter, D. H., Barker, D. F., Nakamura, Y., et al. (1989) · Science · doi:10.1126/science.2649981 · Cited by 2,097
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- Lozano G, 2016, The p53 Protein: From Cell Regulation to Cancer
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Cited by
Sorted by citations
Targeting apoptosis in cancer therapy
Carneiro, B. A., & El‐Deiry, W. S. (2020) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-020-0341-y · Cited by 2,676
p53: 800 million years of evolution and 40 years of discovery
Levine, A. J. (2020) · Nature reviews. Cancer · doi:10.1038/s41568-020-0262-1 · Cited by 876
Self-citationTargeting mutant p53 for cancer therapy: direct and indirect strategies
Hu, J., Cao, J., Topatana, W., Juengpanich, S., Li, S., Zhang, B., Shen, J., Cai, L., Cai, X., & Chen, M. (2021) · Journal of Hematology & Oncology · doi:10.1186/s13045-021-01169-0 · Cited by 576
Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials
Xie, X., Yu, T., Li, X., Zhang, N., Foster, L. J., Peng, C., Huang, W., & He, G. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01589-z · Cited by 396
Targeting p53 for the treatment of cancer
Duffy, M. J., Synnott, N. C., O’Grady, S., & Crown, J. P. (2020) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2020.07.005 · Cited by 355
Metadata
- Authors
- Levine, A. J.
- Affiliations
- Institute for Advanced Study (US)
- Corresponding author
- Levine, Arnold J.
- ORCID
- Levine, Arnold J.
- Venue
- Annual Review of Cancer Biology
- Publisher
- Annual Reviews
- Published
- 2019-03-04
- Volume
- 3
- Issue
- 1
- Pages
- 21-34
- ISSN
- 2472-3428 (ISSN-L)
- OpenAlex
- W2883443537
- Cited by
- 84
- References
- 87
- Citations by year
- 2026: 1 · 2025: 8 · 2024: 3 · 2023: 8 · 2022: 12 · 2021: 30 · 2020: 14 · 2019: 6
- FWCI
- 1.36
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annual Review of Cancer Biology (publishedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute
- 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 › Cancer Research › Cancer Mechanisms and Therapy
- Keywords
- p53, TP53 mutation, p53-targeted therapy, synthetic lethality, cancer immunotherapy, oncolytic viruses, gene therapy
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