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Emerging Role of MDM2 as Target for Anti-Cancer Therapy: A Review

Mohammad F Shaikh1, William F Morano1, John Lee1

  • 1Drexel University College of Medicine, Department of Surgery, Philadelphia, PA, USA.

Annals of Clinical and Laboratory Science
|December 21, 2016
PubMed

Insights

MDM2 (mouse double minute 2 homolog) is a key regulator of the p53 tumor suppressor. Targeting MDM2 offers a dual approach for cancer therapy by inducing apoptosis or causing cancer cell necrosis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • MDM2 (mouse double minute 2 homolog) and its human homolog HDM2 are critical negative regulators of the p53 tumor suppressor protein.
  • Elevated MDM2 expression in cancer cells suppresses p53's pro-apoptotic activity, contributing to tumor development.
  • MDM2 amplification is observed in various cancers, including brain, breast, lung, and soft tissue tumors.

Purpose of the Study:

  • To review the evolving role of MDM2 as a promising anti-cancer therapeutic target.
  • To discuss MDM2's function as a molecular-based tumor biomarker.
  • To explore MDM2-targeted cancer cell death pathways.

Main Methods:

  • Literature review of MDM2's regulatory mechanisms and therapeutic potential.
  • Analysis of MDM2's dual role in p53-dependent and independent cancer cell death.
  • Examination of MDM2's oncogenic properties and biomarker utility.

Main Results:

  • MDM2 regulates p53 through transcriptional blockade and E3 ubiquitin ligase activity.
  • Targeting MDM2-p53 interaction increases p53 levels, inducing cancer cell cycle arrest and apoptosis.
  • Directly targeting MDM2 on cancer cell membranes can induce necrosis via destabilization.

Conclusions:

  • MDM2 is a significant target for novel anti-cancer therapies.
  • MDM2's distinct mechanisms of action offer versatile therapeutic strategies.
  • MDM2 holds potential as a valuable molecular biomarker for cancer diagnosis and prognosis.
Keywords:
HDM2MDM2biomarkersgenomic profilemolecular therapyp53

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