The Cell Cycle: a Key to Unlock EZH2-targeted Therapy Resistance

Cancer Discov. 2024 Jun 3;14(6):903-905. doi: 10.1158/2159-8290.CD-24-0186.

Abstract

In this issue, a study by Kazansky and colleagues explored resistance mechanisms after EZH2 inhibition in malignant rhabdoid tumors (MRT) and epithelioid sarcomas (ES). The study identified genetic alterations in EZH2 itself, along with alterations that converge on RB1-E2F-mediated cell-cycle control, and demonstrated that inhibition of cell-cycle kinases, such as Aurora Kinase B (AURKB) could bypass EZH2 inhibitor resistance to enhance treatment efficacy. See related article by Kazansky et al., p. 965 (6).

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Aurora Kinase B / antagonists & inhibitors
  • Aurora Kinase B / genetics
  • Aurora Kinase B / metabolism
  • Cell Cycle*
  • Drug Resistance, Neoplasm* / genetics
  • Enhancer of Zeste Homolog 2 Protein* / antagonists & inhibitors
  • Enhancer of Zeste Homolog 2 Protein* / genetics
  • Enhancer of Zeste Homolog 2 Protein* / metabolism
  • Humans
  • Molecular Targeted Therapy
  • Polycomb Repressive Complex 2 / antagonists & inhibitors
  • Polycomb Repressive Complex 2 / genetics
  • Polycomb Repressive Complex 2 / metabolism

Substances

  • Antineoplastic Agents
  • Aurora Kinase B
  • Enhancer of Zeste Homolog 2 Protein
  • EZH2 protein, human
  • Polycomb Repressive Complex 2