%0 Journal Article
%T Targeting the MDM2¨Cp53 interaction as a therapeutic strategy for the treatment of cancer
%A Susan K Peirce
%A Harry W Findley
%J Cell Health and Cytoskeleton
%D 2010
%I 
%R http://dx.doi.org/10.2147/CHC.S4952
%X rgeting the MDM2¨Cp53 interaction as a therapeutic strategy for the treatment of cancer Review (4643) Total Article Views Authors: Susan K Peirce, Harry W Findley Published Date June 2010 Volume 2010:2 Pages 49 - 58 DOI: http://dx.doi.org/10.2147/CHC.S4952 Susan K Peirce, Harry W Findley Department of Pediatrics, Division of Hematology and Oncology Emory University School of Medicine, Aflac Cancer Center and Blood Service, Atlanta, Georgia, USA Abstract: The tumor suppressor p53 functions as an important defense against the development of cancer, and is negatively regulated by interaction with the oncogene and E3 ligase MDM2. In a tightly controlled system of feedback, MDM2 is, in turn, inhibited by the tumor suppressor p14ARF. The inhibition of MDM2-p53 interaction is an appealing therapeutic strategy for the treatment of cancer, and significant advances have been made in the development of small-molecule inhibitors which block this interaction and reactivate wild-type p53. However, the p53 gene is frequently mutated or deleted in cancer, or the wild-type p53 function inhibited by high levels of MDM2. Neuroblastoma (NB) is one such cancer and has presented a major therapeutic challenge in pediatric oncology. Although most NB tumors have wild-type p53, the p14ARF/MDM2/p53 pathway is often altered, leading to resistance to many mainstay chemotherapeutics and a high incidence of relapse. In preclinical studies, the MDM2/p53 interaction inhibitor nutlin-3a has shown effectiveness in the treatment of chemoresistant NB with wild-type, mutant or null-p53 status, indicating that nutlin-3a has potential for the treatment of a broad range of chemoresistant and relapse tumors.
%K p53
%K MDM2
%K MDMX
%K TAp73
%K nutlin-3a
%U https://www.dovepress.com/targeting-the-mdm2ndashp53-interaction-as-a-therapeutic-strategy-for-t-peer-reviewed-article-CHC