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Abstract：
Mutations in genes encoding for proteins along the RAS-RAF-MEK-ERK pathway have been detected in a variety of tumor entities including ovarian carcinomas. In the recent years, several inhibitors of this pathway have been developed, whose antitumor potential is currently being assessed in different clinical trials. Low grade serous ovarian carcinoma, is a rare gynecological tumor which shows favorable overall survival, compared to the general ovarian cancer population, but worrying resistance to conventional chemotherapies. The clinical behavior of low grade serous ovarian carcinoma reflects the different gene profile compared to high-grade serous carcinoma: KRAS/BRAF mutations. BRAF inhibitors as single agents were approved for the treatment of BRAF mutated tumors. Nevertheless, many patients face progressive disease. The understanding of the mechanisms of resistance to BRAF inhibitors therapy and preclinical studies showing that BRAF and mitogen-activated protein kinase kinase (MEK) inhibitors combined therapy delays the onset of resistance compared to BRAF inhibitor single agent, led to the clinical investigation of combined therapy. The aim of this paper is to review the efficacy and safety of the combination of BRAF plus MEK inhibitors on ovarian carcinomas, in particularly focusing on low grade serous ovarian carcinoma.
摘要：
已经在包括卵巢癌的多种肿瘤实体中检测到沿着RAS-RAF-MEK-ERK途径编码蛋白质的基因中的突变。近年来,已经开发了这种途径的几种抑制剂，其抗肿瘤潜力目前正在不同的临床试验中进行评估。低级别浆液性卵巢癌，是一种罕见的妇科肿瘤，显示出良好的总体生存率，与普通卵巢癌人群相比，但担心对常规化疗的抵抗力。与高级别浆液性卵巢癌相比，低级别浆液性卵巢癌的临床行为反映了不同的基因谱：KRAS/BRAF突变。作为单一药剂的BRAF抑制剂被批准用于治疗BRAF突变的肿瘤。然而，许多患者面临进行性疾病。对BRAF抑制剂治疗耐药机制的理解和临床前研究表明，与BRAF抑制剂单药相比，BRAF和丝裂原活化蛋白激酶激酶（MEK）抑制剂联合治疗可延迟耐药的发生。导致了综合治疗的临床研究。本文的目的是回顾BRAF联合MEK抑制剂对卵巢癌的疗效和安全性。特别关注低级别浆液性卵巢癌。
