Novel Therapeutic Strategies for Refractory Ovarian Cancers: Clear Cell and Mucinous Carcinomas
Ovarian clear cell and mucinous carcinomas are less sensitive to chemotherapy. This can be explained by carcinogenic mechanisms and molecular biological features. Although chemotherapy with cytotoxic anticancer drugs has been evaluated by clinical studies, none have achieved better treatment outcomes than paclitaxel + carboplatin therapy. In recent years, attention has been focused on treatment with molecular target drugs and immune checkpoint inhibitors that target newly identified biomarkers, and many clinical studies on such treatments have been planned.
Ovarian cancer has the worst prognosis among gynecological cancers. In particular, clear cell and mucinous carcinomas are less sensitive to chemotherapy. The establishment of new therapies is necessary to improve the treatment outcomes for these carcinomas. In previous clinical studies, chemotherapy with cytotoxic anticancer drugs has failed to demonstrate better treatment outcomes than paclitaxel + carboplatin therapy. In recent years, attention has been focused on treatment with molecular target drugs and immune checkpoint inhibitors that target newly identified biomarkers. The issues that need to be addressed include the most appropriate combination of therapies, identifying patients who may benefit from each therapy, and how results should be incorporated into the standard of care for ovarian clear cell and mucinous carcinomas. In this article, we have reviewed the most promising therapies for ovarian clear cell and mucinous carcinomas, which are regarded as intractable, with an emphasis on therapies currently being investigated in clinical studies.
Ovarian cancer is diverse at the molecular level, and clear cell and mucinous carcinomas exhibit low sensitivity to chemotherapy. Although chemotherapy regimens for ovarian clear cell and mucinous carcinomas have been evaluated by numerous clinical studies, they have failed to exhibit treatment outcomes superior to those of TC therapy. The identification of biomarkers and development of therapeutic drugs specific to each type of ovarian cancer are anticipated. For ovarian clear cell carcinoma, in which the PI3K/AKT/mTOR pathway and the MDM2 gene are prognostic factors, AKT and MDM2 inhibitors may prove to be promising therapeutic drugs in the future. The biomakers for ovarian mucinous carcinoma, including the KRAS and HER2-neu genes, MEK, and PI3K, and molecular target drugs such as trastuzumab, lapatinib, and cetuximab have been gaining attention. We hope that molecular target drugs and immune checkpoint inhibitors targeting these genomic alterations will be developed and clinically applied in the future.
卵巢癌在分子水平上是多种多样的，透明细胞癌和粘液癌对化疗的敏感性较低。尽管卵巢透明细胞癌和粘液性癌的化疗方案已通过大量临床研究进行评估，但它们未能表现出优于 TC 治疗的治疗效果。预计针对每种卵巢癌的生物标志物的鉴定和治疗药物的开发。对于卵巢透明细胞癌，其中 PI3K/AKT/mTOR 通路和MDM2基因是预后因素，AKT 和MDM2抑制剂可能被证明是未来有希望的治疗药物。卵巢粘液癌的生物标志物，包括KRAS和HER2-neu基因、MEK、PI3K，以及曲妥珠单抗、拉帕替尼、西妥昔单抗等分子靶向药物备受关注。我们希望未来能够开发出针对这些基因组改变的分子靶向药物和免疫检查点抑制剂并应用于临床。
关键词： 卵巢癌,透明细胞癌,粘液癌,化疗,临床试验,ovarian cancer,clear cell carcinoma,mucinous carcinoma,chemotherapy, clinical trial