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Targeting MDMX for Cancer Therapy: Rationale, Strategies, and Challenges.


ABSTRACT: The oncogene MDMX, also known as MDM4 is a critical negative regulator of the tumor suppressor p53 and has been implicated in the initiation and progression of human cancers. Increasing evidence indicates that MDMX is often amplified and highly expressed in human cancers, promotes cancer cell growth, and inhibits apoptosis by dampening p53-mediated transcription of its target genes. Inhibiting MDMX-p53 interaction has been found to be effective for restoring the tumor suppressor activity of p53. Therefore, MDMX is becoming one of the most promising molecular targets for developing anticancer therapeutics. In the present review, we mainly focus on the current MDMX-targeting strategies and known MDMX inhibitors, as well as their mechanisms of action and in vitro and in vivo anticancer activities. We also propose other potential targeting strategies for developing more specific and effective MDMX inhibitors for cancer therapy.

SUBMITTER: Yu DH 

PROVIDER: S-EPMC7419686 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Targeting MDMX for Cancer Therapy: Rationale, Strategies, and Challenges.

Yu De-Hua DH   Xu Zhi-Yuan ZY   Mo Shaowei S   Yuan Li L   Cheng Xiang-Dong XD   Qin Jiang-Jiang JJ  

Frontiers in oncology 20200805


The oncogene MDMX, also known as MDM4 is a critical negative regulator of the tumor suppressor p53 and has been implicated in the initiation and progression of human cancers. Increasing evidence indicates that MDMX is often amplified and highly expressed in human cancers, promotes cancer cell growth, and inhibits apoptosis by dampening p53-mediated transcription of its target genes. Inhibiting MDMX-p53 interaction has been found to be effective for restoring the tumor suppressor activity of p53.  ...[more]

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