Tamura Ryo, Yoshihara Kosuke, Enomoto Takayuki
Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan.
Cancers (Basel). 2022 Apr 24;14(9):2125. doi: 10.3390/cancers14092125.
Ovarian clear cell carcinoma (OCCC) is associated with chemotherapy resistance and poor prognosis, especially in advanced cases. Although comprehensive genomic analyses have clarified the significance of genomic alterations such as and mutations in OCCC, therapeutic strategies based on genomic alterations have not been confirmed. On the other hand, OCCC is clinically characterized by a high incidence of thromboembolism. Moreover, OCCC specifically shows high expression of tissue factor and interleukin-6, which play a critical role in cancer-associated hypercoagulation and may be induced by OCCC-specific genetic alterations or the endometriosis-related tumor microenvironment. In this review, we focused on the association between cancer-associated hypercoagulation and molecular biology in OCCC. Moreover, we reviewed the effectiveness of candidate drugs targeting hypercoagulation, such as tissue factor- or interleukin-6-targeting drugs, anti-inflammatory drugs, anti-hypoxia signaling drugs, anticoagulants, and combined immunotherapy with these drugs for OCCC. This review is expected to contribute to novel basic research and clinical trials for the prevention, early detection, and treatment of OCCC focused on hypercoagulation.
卵巢透明细胞癌(OCCC)与化疗耐药及预后不良相关,尤其是在晚期病例中。尽管全面的基因组分析已经阐明了OCCC中基因组改变(如 和 突变)的意义,但基于基因组改变的治疗策略尚未得到证实。另一方面,OCCC在临床上的特征是血栓栓塞发生率高。此外,OCCC特别表现出组织因子和白细胞介素-6的高表达,它们在癌症相关的高凝状态中起关键作用,可能由OCCC特异性基因改变或子宫内膜异位症相关的肿瘤微环境诱导。在本综述中,我们重点关注了OCCC中癌症相关高凝状态与分子生物学之间的关联。此外,我们还综述了针对高凝状态的候选药物的有效性,如靶向组织因子或白细胞介素-6的药物、抗炎药、抗缺氧信号药物、抗凝剂以及这些药物与OCCC联合免疫疗法。本综述有望为以高凝状态为重点的OCCC预防、早期检测和治疗的新基础研究和临床试验做出贡献。