Targeting Mouse Double Minute 2: Current Concepts in DNA Damage Repair and Therapeutic Approaches in Cancer

Wen Li1, Xinhao Peng1,2, Jinyi Lang1,2

  • 1Cancer Clinical Research Center & Integrative Cancer Center, Sichuan Cancer Hospital & Institute Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.

Insights

Defects in DNA repair can lead to cancer. This review details how mouse double minute 2 (MDM2) impacts genomic instability by inhibiting p53 and DNA repair proteins, affecting cancer progression and treatment.

Area of Science:

  • Molecular Biology
  • Genetics
  • Oncology

Background:

  • DNA damage repair defects are linked to genome instability and cancer.
  • The tumor suppressor p53 is crucial for cell cycle arrest and DNA repair.
  • The oncoprotein MDM2 inhibits p53 and promotes cancer cell survival and proliferation.

Purpose of the Study:

  • To review the influence of MDM2 on genomic instability.
  • To elucidate MDM2's role in inhibiting p53 and DNA repair.
  • To discuss MDM2's regulatory network and oncogenic functions.

Main Methods:

  • Literature review of MDM2's function in DNA damage response.
  • Analysis of MDM2's interactions with p53 and DNA repair proteins.
  • Examination of MDM2's regulatory network and oncogenic pathways.

Main Results:

  • MDM2 significantly contributes to genomic instability by suppressing p53 and DNA repair.
  • MDM2 regulates its own stability, localization, and transcriptional modifications post-DNA damage.
  • MDM2 exhibits both p53-dependent and independent oncogenic functions.

Conclusions:

  • MDM2 plays a critical role in maintaining genome integrity and cancer development.
  • Targeting the MDM2-p53 axis offers a promising therapeutic strategy for various cancers.
  • Clinical trials investigating MDM2 inhibitors show potential for cancer treatment.

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