New strategies in ovarian cancer treatment
New strategies in ovarian cancer treatment
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DOI：
10.1002/cncr.32544
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发表时间：
2019-12-15
期刊：
影响因子：
6.2
通讯作者：
Kohn, Elise C.
中科院分区：
文献类型：
--
作者：
Lee, Jung-Min;Minasian, Lori;Kohn, Elise C.
剖析输卵管和卵巢癌发生过程的基础科学见解使人们对卵巢癌的起源、分子特征和类型有了更深入的了解。从逻辑上讲，这导致了治疗卵巢癌的新方法的开发。越来越多的新型药物正在被开发以针对不同的生长途径。与不同组织病理学相关的分子标志物的鉴定催生了更新的临床试验设计，以捕获临床和转化终点。 DNA 损伤和修复途径的独特分子特征以及独特的细胞表面标记推动了新药的开发，为铂敏感和铂耐药卵巢癌患者带来了希望。所描述的具体例子包括组织学选择性突变，例如透明细胞癌和子宫内膜样卵巢癌中的 ARID1A；当 p53 介导的细胞周期检查点调节丧失时，使用细胞周期检查点抑制剂的基本原理或同时诱导新抗原形成和释放免疫调节剂的药物组合；以及增强已知药物的治疗递送的技术。在临床试验中需要一种系统且深思熟虑的方法来组合药物，以便无论试验结果如何，结果都能告知临床和转化终点。
Insights from basic science dissecting carcinogenesis in the fallopian tube and ovary have led to a deeper understanding of the origin, molecular characteristics, and types of ovarian cancers. This logically then has led to the development of novel approaches to treat ovarian cancer. Increasingly, novel agents are being developed to target the different growth pathways. The identification of molecular markers associated with different histopathologies has resulted in newer clinical trial designs to capture both clinical and translational endpoints. Unique molecular characteristics in DNA damage and repair pathways and unique cell surface markers have driven new drug development, yielding promise for both patients with platinum-sensitive and platinum-resistant ovarian cancers. Specific examples described include the histology-selective mutations, such as ARID1A in clear cell and endometrioid ovarian cancers; the rationale for using cell cycle checkpoint inhibitors when there already is a p53-mediated loss of cell cycle checkpoint regulation or combinations of agents that will both induce neoantigen formation and unleash immune modulators; and techniques to enhance the therapeutic delivery of known agents. A systematic and thoughtful approach to combining agents in clinical trials is needed so that irrespective of the trial outcomes, the results inform both clinical and translational endpoints.