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Small-molecule MDM2 antagonists reveal aberrant p53 signaling in cancer: Implications for therapy

Tovar, Christian, Rosinski, James, Filipovic, Zoran, Higgins, Brian, Kolinsky, Kenneth, Hilton, Holly, Zhao, Xiaolan, Vu, Binh T., Qing, Weiguo, Packman, Kathryn, Myklebost, Ola, Heimbrook, David C., Vassilev, Lyubomir T.·2006·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.0507493103

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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.

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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
Surfing the p53 network
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-citation
p21 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
The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation
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

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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).

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Translational approaches targeting the p53 pathway for anti‐cancer therapy
Essmann, F., & Schulze‐Osthoff, K. (2012) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2011.01570.x · Cited by 77
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Vu, B. T., & Vassilev, L. T. (2010) · Current topics in microbiology and immunology · doi:10.1007/82_2010_110 · Cited by 82
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Protein Quality Control Degradation in the Nucleus
Enam, C., Geffen, Y., Ravid, T., & Gardner, R. G. (2018) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-062917-012730 · Cited by 75
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Ji, Z., Njauw, C.-N. J., Taylor, M., Neel, V., Flaherty, K. T., & Tsao, H. (2011) · Journal of Investigative Dermatology · doi:10.1038/jid.2011.313 · Cited by 74
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Xiong, S., Van Pelt, C. S., Elizondo-Fraire, A. C., Fernandez-Garcia, B., & Lozano, G. (2007) · Circulation · doi:10.1161/circulationaha.107.689901 · Cited by 71
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Assi, T., Kattan, J. G., Rassy, E., Moussa, T., Nassereddine, H., Honoré, C., Adam, J., Terrier, P., Dumont, S., Mir, O., et al. (2020) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2020.102889 · Cited by 70
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Sullivan, K. D., Padilla-Just, N., Henry, R. E., Porter, C. C., Kim, J., Tentler, J. J., Eckhardt, S. G., Tan, A. C., DeGregori, J., & Espinosa, J. M. (2012) · Nature Chemical Biology · doi:10.1038/nchembio.965 · Cited by 67

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
ORCID: Higgins, Brian
Zhao, Xiaolan
Vu, Binh T.
Packman, Kathryn
Myklebost, Ola
Vassilev, Lyubomir T.
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
DOI: 10.1073/pnas.0507493103
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

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Small-molecule MDM2 antagonists reveal aberrant p53 signaling in cancer: Implications for therapy

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