Clinical Overview of MDM2/X-Targeted Therapies
Andrew Burgess, Kee Ming Chia, Sue Haupt, David Thomas, Ygal Haupt, Elgene Lim
FRONTIERS IN ONCOLOGY | FRONTIERS MEDIA SA | Published : 2016
MDM2 and MDMX are the primary negative regulators of p53, which under normal conditions maintain low intracellular levels of p53 by targeting it to the proteasome for rapid degradation and inhibiting its transcriptional activity. Both MDM2 and MDMX function as powerful oncogenes and are commonly over-expressed in some cancers, including sarcoma (~20%) and breast cancer (~15%). In contrast to tumors that are p53 mutant, whereby the current therapeutic strategy restores the normal active conformation of p53, MDM2 and MDMX represent logical therapeutic targets in cancer for increasing wild-type (WT) p53 expression and activities. Recent preclinical studies suggest that there may also be situati..View full abstract
Awarded by National Breast Cancer Foundation
AB is a CINSW FRL fellow (10/FRL/3-02). KC is an NHMRC Dora Lush Scholar. DT and YH are NHMRC principal research fellows (APP1104364 and APP9628426, respectively). EL is an NBCF/VCA practitioner fellow (PRAC14-002). This work was supported by the Patricia Helen Guest fellowship and Love Your Sister foundation. The funders had no role in analysis, decision to publish, or preparation of the manuscript.