Precision medicine for ovarian clear cell carcinoma based on gene alterations

Int J Clin Oncol. 2020 Mar;25(3):419-424. doi: 10.1007/s10147-020-01622-z. Epub 2020 Feb 4.

Abstract

Ovarian clear cell carcinoma (OCCC) is a histological subtype of epithelial ovarian carcinoma prevalent in Asians. No clear therapeutic selection based on molecular profile has been implemented for this disease. Oncogenic PIK3CA mutation, which activates the PIK3CA/AKT/mTOR signaling pathway, is a promising druggable alteration in OCCC. Recent studies by our group and others have identified the ARID1A mutation as another alteration linked to therapeutic selection based on synthetic lethality: deleterious ARID1A mutations, resulting in ARID1A deficiency, make OCCC cells sensitive to drugs targeting poly (ADP-ribose) polymerase and EZH2, as well as to glutathione inhibitors. In addition, we recently obtained evidence that ARID1A-deficient OCCC could benefit from gemcitabine treatment. Precision medicine based on gene alteration profiling might improve the prognosis of OCCC patients.

Keywords: Gemcitabine; Immune checkpoint inhibitory therapy; Ovarian clear cell carcinoma; Precision medicine; Synthetic lethality.

Publication types

  • Review

MeSH terms

  • Adenocarcinoma, Clear Cell / drug therapy*
  • Adenocarcinoma, Clear Cell / genetics*
  • Adenocarcinoma, Clear Cell / pathology
  • Antimetabolites, Antineoplastic / pharmacology
  • Class I Phosphatidylinositol 3-Kinases / genetics
  • Class I Phosphatidylinositol 3-Kinases / metabolism
  • DNA-Binding Proteins / genetics
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / pharmacology
  • Enhancer of Zeste Homolog 2 Protein / genetics
  • Enhancer of Zeste Homolog 2 Protein / metabolism
  • Female
  • Gemcitabine
  • Gene Dosage
  • Glutathione / antagonists & inhibitors
  • Humans
  • Molecular Targeted Therapy / methods
  • Mutation
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / pathology
  • Precision Medicine / methods*
  • Transcription Factors / genetics

Substances

  • ARID1A protein, human
  • Antimetabolites, Antineoplastic
  • DNA-Binding Proteins
  • Transcription Factors
  • Deoxycytidine
  • EZH2 protein, human
  • Enhancer of Zeste Homolog 2 Protein
  • Class I Phosphatidylinositol 3-Kinases
  • PIK3CA protein, human
  • Glutathione
  • Gemcitabine