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Polycomb repressor complex: Its function in human cancer and therapeutic target strategy

Jingrong Liu1, Hongjie Fan1, Xinmiao Liang2

  • 1Ganjiang Chinese Medicine Innovation Center, Nanchang 330000, China.

Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie
|November 19, 2023
PubMed

Insights

The Polycomb Repressor Complex (PRC) is crucial for gene regulation and implicated in cancer. Targeting PRC, especially with EZH2 inhibitors, shows therapeutic promise, but combination therapies may be needed for greater efficacy.

Area of Science:

  • Epigenetics and Molecular Biology
  • Cancer Biology
  • Pharmacology

Background:

  • The Polycomb Repressor Complex (PRC) is essential for developmental gene regulation.
  • PRC dysregulation is a significant factor in the development of various human cancers.
  • PRC interacts with cellular signaling pathways, influencing cancer complexity.

Purpose of the Study:

  • To review the critical role of PRC in gene regulation, focusing on Polycomb group (PcG) proteins and chromatin compaction via phase separation.
  • To highlight the pathological implications of PRC dysregulation in tumors and the mechanisms driving cancer progression.
  • To discuss current and future therapeutic strategies targeting PRC, including EZH2 inhibitors and combination therapies.

Main Methods:

  • Literature review focusing on PRC function, dysregulation in cancer, and therapeutic interventions.
  • Analysis of mechanisms involving PcG proteins, chromatin compaction, and phase separation.
  • Evaluation of preclinical and clinical data for PRC-targeted therapies, particularly EZH2 inhibitors.

Main Results:

  • PRC complex, through PcG proteins, mediates gene silencing via chromatin compaction and phase separation.
  • PRC dysregulation is linked to the progression of multiple tumor types.
  • EZH2 inhibitors represent a significant advancement in PRC-targeted cancer therapy.

Conclusions:

  • PRC plays a vital role in both normal development and cancer pathogenesis.
  • Targeting PRC offers promising therapeutic avenues for cancer treatment.
  • Combination therapies are likely necessary to maximize the efficacy of PRC-targeted treatments.
Keywords:
Cancer progressionEpigenetic modificationPolycomb repressor complexTherapeutic targetTumorigenesis

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