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Molecular pathways: targeting Mdm2 and Mdm4 in cancer therapy.

Authors: Li, Q  Lozano, G 
Citation: Li Q and Lozano G, Clin Cancer Res. 2013 Jan 1;19(1):34-41. doi: 10.1158/1078-0432.CCR-12-0053. Epub 2012 Dec 21.
Pubmed: (View Article at PubMed) PMID:23262034
DOI: Full-text: DOI:10.1158/1078-0432.CCR-12-0053

The p53 tumor suppressor is activated in response to cellular stresses to induce cell-cycle arrest, cellular senescence, and apoptosis. The p53 gene is inactivated by mutations in more than 50% of human tumors. In addition, tumor cells dampen p53 activities via overexpression of p53-negative regulators, in particular 2 structurally related proteins, Mdm2 and Mdm4. And yet, Mdm2 and Mdm4 possess p53-independent activities, which also contribute to tumor formation and progression. Given that Mdm2 and Mdm4 inhibit p53 activities to promote tumor development, small molecules and peptides were developed to abrogate the inhibition of p53 by Mdm proteins. Antitumor activities of these molecules have already been confirmed in preclinical studies and early-phase clinical trials. These research endeavors and clinical advances constitute the main focus of this review.

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Molecular Pathway Annotations
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CRRD Object Information
CRRD ID: 8663434
Created: 2014-07-02
Species: All species
Last Modified: 2014-07-02
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.