TY - JOUR
T1 - Molecular pathways
T2 - Targeting Mdm2 and Mdm4 in cancer therapy
AU - Li, Qin
AU - Lozano, Guillermina
PY - 2013/1/1
Y1 - 2013/1/1
N2 - 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 byMdmproteins. 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.
AB - 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 byMdmproteins. 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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U2 - 10.1158/1078-0432.CCR-12-0053
DO - 10.1158/1078-0432.CCR-12-0053
M3 - Article
C2 - 23262034
AN - SCOPUS:84871980628
SN - 1078-0432
VL - 19
SP - 34
EP - 41
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 1
ER -