The DOI matches its Crossref record; 36 of the 36 references it cites were found in a registry or an index.
Small-molecule MDM2 antagonists reveal aberrant p53 signaling in cancer: Implications for therapy
Abstract
The p53 tumor suppressor retains its wild-type conformation and transcriptional activity in half of all human tumors, and its activation may offer a therapeutic benefit. However, p53 function could be compromised by defective signaling in the p53 pathway. Using a small-molecule MDM2 antagonist, nutlin-3, to probe downstream p53 signaling we find that the cell-cycle arrest function of the p53 pathway is preserved in multiple tumor-derived cell lines expressing wild-type p53, but many have a reduced ability to undergo p53-dependent apoptosis. Gene array analysis revealed attenuated expression of multiple apoptosis-related genes. Cancer cells with mdm2 gene amplification were most sensitive to nutlin-3 in vitro and in vivo , suggesting that MDM2 overexpression may be the only abnormality in the p53 pathway of these cells. Nutlin-3 also showed good efficacy against tumors with normal MDM2 expression, suggesting that many of the patients with wild-type p53 tumors may benefit from antagonists of the p53–MDM2 interaction.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Restoration of p53 is known to block cell-cycle progression and induces apoptosis in the presence of MDM2-p53 interaction antagonists [43–45].”
From Restoration of p53 using the novel MDM2-p53 antagonist APG115 suppresses dedifferentiated papillary thyroid cancer cells (2017) · cites this paper as [43]
In the citing paper
“the MDM2 antagonist nutlin 3a (discussed below) is well-tolerated in mouse preclinical models84.”
From MDM2, MDMX and p53 in oncogenesis and cancer therapy (2013) · cites this paper as [84]
In the citing paper
“Nutlin profoundly decreased the viability of SJSA cells, as reported previously26”
From CDK4 inhibition diminishes p53 activation by MDM2 antagonists (2018) · cites this paper as [26]
Citations
Cites
WAF1, a potential mediator of p53 tumor suppression
El-Deiry, W. S., Tokino, T., Velculescu, V. E., Levy, D. B., Parsons, R., Trent, J. M., Lin, D., Mercer, W. E., Kinzler, K. W., & Vogelstein, B. (1993) · Cell · doi:10.1016/0092-8674(93)90500-p · Cited by 8,321
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
p53, the cellular gatekeeper for growth and division
Levine, A. J. (1997) · Cell · doi:10.1016/s0092-8674(00)81871-1 · Cited by 7,693
Vogelstein, B., Lane, D., & Levine, A. J. (2000) · Nature · doi:10.1038/35042675 · Cited by 6,607
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
Self-citationp21 is a universal inhibitor of cyclin kinases
Xiong, Y., Hannon, G., Zhang, H., Casso, D., Kobayashi, R., & Beach, D. (1993) · Nature · doi:10.1038/366701a0 · Cited by 3,691
Live or let die: the cell's response to p53
Vousden, K. H., & Lü, X. (2002) · Nature reviews. Cancer · doi:10.1038/nrc864 · Cited by 3,231
Momand, J., Zambetti, G. P., Olson, D. C., George, D., & Levine, A. J. (1992) · Cell · doi:10.1016/0092-8674(92)90644-r · Cited by 3,113
Requirement for p53 and p21 to Sustain G 2 Arrest After DNA Damage
Bunz, F., Dutriaux, A., Lengauer, C., Waldman, T., Zhou, S., Brown, J. P., Sedivy, J. M., Kinzler, K. W., & Vogelstein, B. (1998) · Science · doi:10.1126/science.282.5393.1497 · Cited by 2,803
The p53 pathway: positive and negative feedback loops
Harris, S. L., & Levine, A. J. (2005) · Oncogene · doi:10.1038/sj.onc.1208615 · Cited by 1,967
Research works printed but not linked: 4
- K. H. Vousden, C. Prives Cell 120, 7–10 (2005).
- D. P. Steensma, M. Timm, T. E. Witzig Methods Mol. Med 85, 323–332 (2003).
- K. Satyamoorthy, N. H. Chehab, M. J. Waterman, M. C. Lien, W. S. El-Deiry, M. Herlyn, T. D. Halazonetis Cell Growth Differ 11, 467–474 (2000).
- H. Yang, Z. Filipovic, D. Brown, S. N. Breit, L. T. Vassilev Mol. Cancer Ther 2, 1023–1029 (2003).
Cited by
Sorted by citations
Standards and Guidelines for the Interpretation and Reporting of Sequence Variants in Cancer
Li, M. M., Datto, M., Duncavage, E. J., Kulkarni, S., Lindeman, N. I., Roy, S., Tsimberidou, A. M., Vnencak‐Jones, C. L., Wolff, D. J., Younes, A., et al. (2016) · Journal of Molecular Diagnostics · doi:10.1016/j.jmoldx.2016.10.002 · Cited by 2,113
Kruse, J.-P., & Gu, W. (2009) · Cell · doi:10.1016/j.cell.2009.04.050 · Cited by 1,610
Transcriptional Activation of miR-34a Contributes to p53-Mediated Apoptosis
Raver-Shapira, N., Marciano, E., Meiri, E., Spector, Y., Rosenfeld, N., Moskovits, N. B.-C., Bentwich, Z., & Oren, M. (2007) · Molecular Cell · doi:10.1016/j.molcel.2007.05.017 · Cited by 1,365
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
The Cell–Cycle Arrest and Apoptotic Functions of p53 in Tumor Initiation and Progression
Chen, J. (2016) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a026104 · Cited by 1,222
Metadata
- Authors
- Tovar, C., Rosinski, J., Filipovic, Z., Higgins, B., Kolinsky, K., Hilton, H., Zhao, X., Vu, B. T., Qing, W., Packman, K., Myklebost, O., Heimbrook, D. C., & Vassilev, L. T.
- Affiliations
- *Roche Research Center, Hoffmann-La Roche Inc., Nutley, NJ 07110; and
- F. Hoffmann-La Roche AG (CH)
- Institute for Cancer Research, Norwegian Radium Hospital, 0310 Oslo, Norway
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2006-01-27
- Volume
- 103
- Issue
- 6
- Pages
- 1888-1893
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W1993263392
- Cited by
- 708
- References
- 36
- Citations by year
- 2026: 17 · 2025: 24 · 2024: 15 · 2023: 39 · 2022: 23 · 2021: 27 · 2020: 25 · 2019: 33 · 2018: 20 · 2017: 27 · 2016: 44 · 2015: 39 · 2014: 45 · 2013: 39 · 2012: 47
- FWCI
- 25.66
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- MDM2 inhibitors, Nutlin-3, p53 pathway, p53-dependent apoptosis, cell cycle arrest, MDM2 amplification, p53-MDM2 interaction, apoptosis-related gene expression, cancer therapy
- MeSH terms
- Animals, Antineoplastic Agents, Cell Cycle, Cell Line, Humans, Imidazoles, Mice, Nude, Neoplasms, Piperazines, Signal Transduction, Gene Expression Regulation, Neoplastic, Tumor Suppressor Protein p53, Gene Expression Profiling, Xenograft Model Antitumor Assays, Mice, Proto-Oncogene Proteins c-mdm2
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
