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

Frontiers in Oncology
De-Hua YuJiang-Jiang Qin

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.

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Methods Mentioned

BETA
the
ubiquitination
neddylation
xenograft
transfection
deubiquitination

Related Concepts

Antineoplastic Agents
Malignant Neoplasms
Cell Growth
Genes
Oncogenes
Transcription, Genetic
TP53 gene
Tumor Suppressor Genes
Protein p53
Mdm2 protein

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