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Precision medicine for ovarian clear cell carcinoma based on gene alterations

Journal

INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY
Volume 25, Issue 3, Pages 419-424

Publisher

SPRINGER JAPAN KK
DOI: 10.1007/s10147-020-01622-z

Keywords

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

Categories

Funding

  1. National Cancer Center Research and Development Fund [30-A-6]

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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.

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