Department of Obstetrics and Gynecology, The Jikei University School of Medicine, Tokyo, Japan.
Division of Genome Biology, National Cancer Center Research Institute, Tokyo, Japan.
Int J Clin Oncol. 2020 Mar;25(3):419-424. doi: 10.1007/s10147-020-01622-z. Epub 2020 Feb 4.
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.
卵巢透明细胞癌（OCCC）是一种上皮性卵巢癌的组织学亚型，在亚洲人群中较为常见。目前针对这种疾病，还没有基于分子谱的明确治疗选择。致癌性 PIK3CA 突变激活了 PIK3CA/AKT/mTOR 信号通路，是 OCCC 一种有前途的可用药变。最近，我们团队和其他团队的研究发现 ARID1A 突变是另一种与基于合成致死性的治疗选择相关的改变：有害的 ARID1A 突变导致 ARID1A 缺失，使 OCCC 细胞对聚（ADP-核糖）聚合酶和 EZH2 的靶向药物以及谷胱甘肽抑制剂敏感。此外，我们最近获得的证据表明，ARID1A 缺陷型 OCCC 可能受益于吉西他滨治疗。基于基因改变谱的精准医学可能会改善 OCCC 患者的预后。
