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

Biomed Pharmacother. 2023 Dec 31:169:115897. doi: 10.1016/j.biopha.2023.115897. Epub 2023 Nov 17.

Abstract

The Polycomb Repressor Complex (PRC) plays a pivotal role in gene regulation during development and disease, with dysregulation contributing significantly to various human cancers. The intricate interplay between PRC and cellular signaling pathways sheds light on cancer complexity. PRC presents promising therapeutic opportunities, with inhibitors undergoing rigorous evaluation in preclinical and clinical studies. In this review, we emphasize the critical role of PRC complex in gene regulation, particularly PcG proteins mediated chromatin compaction through phase separation. We also highlight the pathological implications of PRC complex dysregulation in various tumors, elucidating underlying mechanisms driving cancer progression. The burgeoning field of therapeutic strategies targeting PRC complexes, notably EZH2 inhibitors, has advanced significantly. However, we explore the need for combination therapies to enhance PRC targeted treatments efficacy, providing a glimpse into the future of cancer therapeutics.

Keywords: Cancer progression; Epigenetic modification; Polycomb repressor complex; Therapeutic target; Tumorigenesis.

Publication types

  • Review

MeSH terms

  • Chromatin
  • Enhancer of Zeste Homolog 2 Protein / metabolism
  • Humans
  • Neoplasms* / metabolism
  • Polycomb Repressive Complex 1 / genetics
  • Polycomb Repressive Complex 2* / genetics
  • Polycomb-Group Proteins / genetics

Substances

  • Polycomb Repressive Complex 2
  • Enhancer of Zeste Homolog 2 Protein
  • Polycomb-Group Proteins
  • Chromatin
  • Polycomb Repressive Complex 1