Cited by 710Cancer-related Molecular PathwaysHeat shock proteins researchCell death mechanisms and regulation

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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

Show all 36 references

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).

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Zauli, G., Rimondi, E., Corallini, F., Fadda, R., Capitani, S., & Secchiero, P. (2007) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.070618 · Cited by 29
Mdm4 loss in the intestinal epithelium leads to compartmentalized cell death but no tissue abnormalities
Valentin-Vega, Y. A., Box, N., Terzian, T., & Lozano, G. (2009) · Differentiation · doi:10.1016/j.diff.2009.03.001 · Cited by 28
Catalytic Asymmetric Synthesis of Spirooxindoles by a Mannich‐Type Reaction of Isothiocyanato Oxindoles
Kato, S., Yoshino, T., Shibasaki, M., Kanai, M., & Matsunaga, S. (2012) · Angewandte Chemie · doi:10.1002/ange.201203005 · Cited by 28
Impact of allogeneic haematopoietic stem cell transplantation in patients with abnl(17p) acute myeloid leukaemia
Mohr, B., Schetelig, J., Schäfer‐Eckart, K., Schmitz, N., Hänel, M., Rösler, W., Frickhofen, N., Link, H., Neubauer, A., Schuler, U. S., et al. (2013) · British Journal of Haematology · doi:10.1111/bjh.12253 · Cited by 28
Modulating the p53 pathway
Dey, A., Lane, D. P., & Verma, C. S. (2010) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2010.02.004 · Cited by 27
Improving anticancer activity towards colon cancer cells with a new p53‐activating agent
Raimundo, L., Espadinha, M., Soares, J., Loureiro, J. B., Alves, M. G., Santos, M. M. M., & Saraiva, L. (2018) · British Journal of Pharmacology · doi:10.1111/bph.14468 · Cited by 28
Retraction notice to “Epithelial cell adhesion molecule targeted nutlin-3a loaded immunonanoparticles for cancer therapy” [Acta Biomaterialia 7 (2011) 355–369]
Das, M., & Sahoo, S. K. (2010) · Acta Biomaterialia · doi:10.1016/j.actbio.2010.08.010 · Cited by 29
Retracted
Discussion of some ‘knowns’ and some ‘unknowns’ about the tumour suppressor p53
Lieschke, E., Wang, Z., Kelly, G. L., & Strasser, A. (2018) · Journal of Molecular Cell Biology · doi:10.1093/jmcb/mjy077 · Cited by 29
Inhibition of p53-MDM2 binding reduces senescent cell abundance and improves the adaptive responses of skeletal muscle from aged mice
Nolt, G. L., Keeble, A. R., Wen, Y., Strong, A. C., Thomas, N. T., Valentino, T. R., Brightwell, C. R., Murach, K. A., Patrizia, S., Weinstabl, H., et al. (2023) · GeroScience · doi:10.1007/s11357-023-00976-2 · Cited by 27
Comparative validated molecular modeling of p53-HDM2 inhibitors as antiproliferative agents
Mondal, C., Halder, A. K., Adhikari, N., Saha, A., Saha, K. D., Gayen, S., & Jha, T. (2014) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2014.12.011 · Cited by 27
Cross Talk Networks of Mammalian Target of Rapamycin Signaling With the Ubiquitin Proteasome System and Their Clinical Implications in Multiple Myeloma
Eichner, R., Fernández‐Sáiz, V., Targosz, B., & Bassermann, F. C. (2018) · International review of cytology · doi:10.1016/bs.ircmb.2018.06.001 · Cited by 27
Mechanisms of TP53 Pathway Inactivation in Embryonic and Somatic Cells—Relevance for Understanding (Germ Cell) Tumorigenesis
Timmerman, D. M., Remmers, T. L., Hillenius, S., & Looijenga, L. H. J. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22105377 · Cited by 26
MDM2 antagonist nutlin-3a reverses mitoxantrone resistance by inhibiting breast cancer resistance protein mediated drug transport
Zhang, F., Throm, S. L., Murley, L. L., Miller, L. A., Zatechka, D. S., Guy, R. K., Kennedy, R. M., & Stewart, C. F. (2011) · Biochemical Pharmacology · doi:10.1016/j.bcp.2011.03.024 · Cited by 27
Increased aldehyde reductase expression mediates acquired radioresistance of laryngeal cancer cells via modulating p53
Kim, J., Chang, J. W., Park, J. K., & Hwang, S. (2012) · Cancer Biology & Therapy · doi:10.4161/cbt.20081 · Cited by 27
Bone Sarcomas: From Biology to Targeted Therapies
Gaspar, N., Giannatale, A. D., Geoerger, B., Rédiní, F., Corradini, N., Entz‐Werlé, N., Tirode, F., Marec‐Bérard, P., Gentet, J., Laurence, V., et al. (2012) · Sarcoma · doi:10.1155/2012/301975 · Cited by 28
Initial testing of JNJ‐26854165 (Serdemetan) by the pediatric preclinical testing program
Smith, M. A., Gorlick, R., Kolb, E. A., Lock, R., Carol, H., Maris, J. M., Keir, S. T., Morton, C. L., Reynolds, C. P., Kang, M. H., et al. (2012) · Pediatric Blood & Cancer · doi:10.1002/pbc.23319 · Cited by 26
Treatment of De-Differentiated Liposarcoma in the Era of Immunotherapy
Zhou, M. Y., Bui, N. Q., Charville, G. W., Ganjoo, K. N., & Pan, M. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24119571 · Cited by 29
Targeting IRES-Mediated p53 Synthesis for Cancer Diagnosis and Therapeutics
Ji, B., Harris, B., Liu, Y., Deng, Y., Gradilone, S. A., Cleary, M. P., Liu, J., & Yang, D. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18010093 · Cited by 26
Untitled work
(2008) · PubMed · Cited by 26
Histone deacetylase inhibitors enhance the anticancer activity of nutlin-3 and induce p53 hyperacetylation and downregulation of MDM2 and MDM4 gene expression
Palani, C. D., Beck, J. F., & Sonnemann, J. (2010) · Investigational New Drugs · doi:10.1007/s10637-010-9510-7 · Cited by 26
Reactivation of p53 function in synovial sarcoma cells by inhibition of p53–HDM2 interaction
D’Arcy, P., Ryan, B. A., & Brodin, B. A. (2009) · Cancer Letters · doi:10.1016/j.canlet.2008.10.030 · Cited by 26
Discovery of novel polycyclic spiro-fused carbocyclicoxindole-based anticancer agents
Zhang, L., Ren, W. T., Wang, X., Zhang, J., Liu, J., Zhao, L., & Zhang, X. (2016) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2016.12.021 · Cited by 25
2,4,5-Tris(alkoxyaryl)imidazoline derivatives as potent scaffold for novel p53-MDM2 interaction inhibitors: Design, synthesis, and biological evaluation
Bazanov, D. R., Pervushin, N. V., Savitskaya, V. Y., Аникина, Л. В., Proskurnina, M. V., Lozinskaya, N. A., & Kopeina, G. S. (2019) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2019.06.007 · Cited by 25
Ribosome biogenesis is a downstream effector of the oncogenic U2AF1-S34F mutation
Akef, A., McGraw, K. R., Cappell, S. D., & Larson, D. R. (2020) · PLoS Biology · doi:10.1371/journal.pbio.3000920 · Cited by 25
DAB2IP suppresses tumor malignancy by inhibiting GRP75-driven p53 ubiquitination in colon cancer
Feng, S., Huang, Q., Deng, J., Jia, W., Gong, J., Xie, D., Shen, J., & Liu, L. (2022) · Cancer Letters · doi:10.1016/j.canlet.2022.215588 · Cited by 25
Construction of contiguous tetrasubstituted chiral carbon stereocenters via direct catalytic asymmetric aldol and mannich‐type reactions
Matsunaga, S., & Yoshino, T. (2011) · The Chemical Record · doi:10.1002/tcr.201100020 · Cited by 25
Inhibition of the p53–MDM2 interaction by adenovirus delivery of ribosomal protein L23 stabilizes p53 and induces cell cycle arrest and apoptosis in gastric cancer
Zhang, Y., Shi, Y., Li, X., Du, W., Luo, G., Gou, Y., Wang, X., Guo, X., Liu, J., Ding, J., et al. (2009) · The Journal of Gene Medicine · doi:10.1002/jgm.1424 · Cited by 26
Organelle-Targeted Delivery of Biological Macromolecules Using the Protein Transduction Domain: Potential Applications for Peptide Aptamer Delivery into the Nucleus
Yoshikawa, T., Sugita, T., Mukai, Y., Yamanada, N., Nagano, K., Nabeshi, H., Yoshioka, Y., Nakagawa, S., Abe, Y., Kamada, H., et al. (2008) · Journal of Molecular Biology · doi:10.1016/j.jmb.2008.05.047 · Cited by 25
RG7112, a Small-Molecule Inhibitor of MDM2, Enhances Trabectedin Response in Soft Tissue Sarcomas
Obrador-Hevia, A., Martinez-Font, E., Felipe-Abrio, I., Calabuig-Fariñas, S., Serra-Sitjar, M., López-Guerrero, J. A., Ramos, R., Alemany, R., & Martín-Broto, J. (2015) · Cancer Investigation · doi:10.3109/07357907.2015.1064534 · Cited by 24
BRAF V600E in cancer: Exploring structural complexities, mutation profiles, and pathway dysregulation
Bharti, J., Gogu, P., Pandey, S. K., Verma, A., Yadav, J. P., Singh, A. K., Kumar, P., Dwivedi, A. R., & Pathak, P. (2025) · Experimental Cell Research · doi:10.1016/j.yexcr.2025.114440 · Cited by 28

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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