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上皮性卵巢癌:精准医学时代的治疗进展。

Epithelial ovarian cancer: Evolution of management in the era of precision medicine.

机构信息

Clinician Investigator, Bras Drug Development Program; and Staff Medical Oncologist and Gynecology Site Leader, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.

Assistant Professor, University of Toronto, Toronto, ON, Canada.

出版信息

CA Cancer J Clin. 2019 Jul;69(4):280-304. doi: 10.3322/caac.21559. Epub 2019 May 17.

Abstract

Ovarian cancer is the second most common cause of gynecologic cancer death in women around the world. The outcomes are complicated, because the disease is often diagnosed late and composed of several subtypes with distinct biological and molecular properties (even within the same histological subtype), and there is inconsistency in availability of and access to treatment. Upfront treatment largely relies on debulking surgery to no residual disease and platinum-based chemotherapy, with the addition of antiangiogenic agents in patients who have suboptimally debulked and stage IV disease. Major improvement in maintenance therapy has been seen by incorporating inhibitors against poly (ADP-ribose) polymerase (PARP) molecules involved in the DNA damage-repair process, which have been approved in a recurrent setting and recently in a first-line setting among women with BRCA1/BRCA2 mutations. In recognizing the challenges facing the treatment of ovarian cancer, current investigations are enlaced with deep molecular and cellular profiling. To improve survival in this aggressive disease, access to appropriate evidence-based care is requisite. In concert, realizing individualized precision medicine will require prioritizing clinical trials of innovative treatments and refining predictive biomarkers that will enable selection of patients who would benefit from chemotherapy, targeted agents, or immunotherapy. Together, a coordinated and structured approach will accelerate significant clinical and academic advancements in ovarian cancer and meaningfully change the paradigm of care.

摘要

卵巢癌是全球女性中第二大常见的妇科癌症死亡原因。其预后较为复杂,因为该疾病通常被诊断较晚,并且由几种具有不同生物学和分子特性的亚型组成(即使在同一组织学亚型内),而且治疗的可及性和可获得性存在不一致。初始治疗主要依赖于尽可能地减瘤手术和铂类化疗,对于减瘤不充分和 IV 期疾病的患者,添加抗血管生成药物。通过将参与 DNA 损伤修复过程的多聚(ADP-核糖)聚合酶(PARP)分子抑制剂纳入维持治疗,已经在复发性疾病中得到了显著改善,并且最近在 BRCA1/BRCA2 突变的女性的一线治疗中得到了批准。在认识到卵巢癌治疗所面临的挑战时,目前的研究与深入的分子和细胞分析相结合。为了提高这种侵袭性疾病的生存率,需要获得适当的循证护理。同时,实现个体化精准医学需要优先考虑创新治疗的临床试验,并完善预测生物标志物,以便选择从化疗、靶向药物或免疫治疗中受益的患者。通过协调一致的方法,将加速卵巢癌的重大临床和学术进展,并显著改变护理模式。

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