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Evolution of Chemosensitivity and Resistance Assays as Predictors of Clinical Outcomes in Epithelial Ovarian Cancer Patients

机译:化学敏感性和抗药性测定法在卵巢上皮癌患者临床疗效预测中的发展

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摘要

Epithelial ovarian cancer (EOC) is responsible for more cancer-related deaths than any other malignancy of the female reproductive system. The standard of care for advanced EOC involves a combination of cytoreductive surgery and platinum-based chemotherapy. Although a majority of patients respond to a platinum-containing regimen, many fail to respond to first-line treatment (platinum-refractory disease) or experience disease progression within 6 months of completing treatment (platinum-resistant disease). Even in patients who initially respond to platinum-based therapy, secondary development of platinum resistance is common. Many chemotherapeutic regimens with comparable efficacy and toxicities are available, leaving the determination of optimal therapy to the physician’s discretion.There have been many efforts over the years to develop accurate predictors of outcomes in patients treated with chemotherapy to help inform treatment decisions. Predictive treatment markers are particularly relevant in a disease such as EOC, where a large number of similarly efficacious chemotherapy regimens are available. Chemosensitivity and resistance assays (CSRAs) are attractive approaches to interrogate the efficacy and complex biology of EOC. Some early predictive cellular tests, such as the early clonogenic assays, were limited by technical and logistical issues. Over time, changes in these assays have improved their prognostic and predictive value, but there is still a lack of widespread adoption due to methodological difficulties or limited clinical validation. Herein, we provide an overview of the evolution of CSRAs used to predict outcomes in patients treated with chemotherapy that have been evaluated for use in EOC, with a focus on the latest generation chemoresponse assay.
机译:上皮性卵巢癌(EOC)比女性生殖系统的任何其他恶性肿瘤造成的与癌症相关的死亡更多。晚期EOC的护理标准涉及细胞减灭术和铂类化学疗法的结合。尽管大多数患者对含铂的治疗方案有反应,但许多患者对一线治疗(铂难治性疾病)无反应或在完成治疗后6个月内经历疾病进展(铂抗性疾病)。即使在最初对铂类疗法产生反应的患者中,铂耐药性的继发性发展也是常见的。有许多疗效和毒性可比的化疗方案可供选择,这取决于最佳医师的判断。多年来,人们一直在努力开发准确的化疗结果预测指标,以帮助制定治疗方案。预测性治疗标志物与诸如EOC之类的疾病特别相关,在EOC中,可以使用大量类似有效的化疗方案。化学敏感性和耐药性分析(CSRA)是审视EOC的功效和复杂生物学的诱人方法。一些早期的预测性细胞试验,例如早期的克隆形成试验,受到技术和后勤问题的限制。随着时间的流逝,这些检测方法的改变已经改善了它们的预后和预测价值,但是由于方法学上的困难或有限的临床验证,仍然缺乏广泛的采用。在此,我们概述了CSRA的发展,这些CSRA用来预测已评估用于EOC的化疗患者的结局,重点是最新一代的化学反应分析。

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