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卵巢癌铂耐药的生物标志物:我们可以用什么来改善治疗。

Biomarkers of platinum resistance in ovarian cancer: what can we use to improve treatment.

机构信息

Hunter Medical Research Institute, Newcastle, New South Wales, Australia.

School of Medicine and Public Health, Faculty of Health and Medicine, University of Newcastle, New South Wales, Australia.

出版信息

Endocr Relat Cancer. 2018 May;25(5):R303-R318. doi: 10.1530/ERC-17-0336. Epub 2018 Feb 27.

Abstract

Ovarian cancer has poor survival rates due to a combination of diagnosis at advanced disease stages and disease recurrence as a result of platinum chemotherapy resistance. High-grade serous ovarian cancer (HGSOC), the most common ovarian cancer subtype, is conventionally treated with surgery and paclitaxel/carboplatin combination chemotherapy. Initial response rates are 60-80%, but eventually the majority of patients become platinum-resistant with subsequent relapses. Extensive research on individual biomarkers of platinum resistance has revealed many potential targets for the development new treatments. While this is ongoing, there are also epigenetic, DNA repair, genome and immune changes characterised in platinum-resistant HGSOC that can be targeted with current therapies. This review discusses biomarkers of platinum chemotherapy resistance in ovarian cancer with a focus on biomarkers that are targetable with alternative treatment combinations to those currently used. After decades of research focused on elucidating the biological cause of platinum resistance, future research needs to focus on using this knowledge to overcome resistance for patients with ovarian cancer.

摘要

由于诊断时疾病已处于晚期和铂类化疗耐药导致疾病复发的综合原因,卵巢癌的存活率较差。高级别浆液性卵巢癌(HGSOC)是最常见的卵巢癌亚型,传统上采用手术和紫杉醇/卡铂联合化疗进行治疗。初始缓解率为 60-80%,但最终大多数患者因铂类耐药而随后复发。对铂类耐药的个体生物标志物的广泛研究揭示了许多开发新治疗方法的潜在靶点。虽然这正在进行中,但在铂类耐药性 HGSOC 中也存在表观遗传、DNA 修复、基因组和免疫变化,可以用当前的治疗方法来靶向这些变化。本综述讨论了卵巢癌铂类化疗耐药的生物标志物,重点讨论了那些可以通过与目前使用的治疗方案不同的治疗方案来靶向的生物标志物。经过几十年的研究集中阐明了铂类耐药的生物学原因,未来的研究需要集中利用这些知识来克服卵巢癌患者的耐药性。

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