Erythropoiesis-stimulating agent use in cancer: Preclinical and clinical perspectives
Erythropoiesis-stimulating agent use in cancer: Preclinical and clinical perspectives
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DOI：
10.1158/1078-0432.ccr-08-0264
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发表时间：
2008-08-01
影响因子：
11.5
通讯作者：
Arcasoy, Murat O.
中科院分区：
文献类型：
--
作者：
Arcasoy, Murat O.
在最近的一系列临床试验中，用于治疗癌症患者化疗引起的贫血的红细胞生成刺激剂（ESA）与肿瘤进展加速和生存受损的不良后果相关。随着癌症患者 ESA 给药的临床实践指南不断发展以提高安全性，不良结果的潜在机制以及 ESA 是否对原发性肿瘤发挥直接和/或间接作用以调节肿瘤细胞生长、存活和放化疗反应仍不确定。肿瘤细胞中促红细胞生成素受体 (EpoR) 的表达提出了一种简单化的可能性：通过功能性细胞受体介导的 Epo 信号传导可能以直接方式促进肿瘤进展。然而，癌症中的 Epo 生物学可能很复杂，多种因素的相互作用可能参与肿瘤对外源 Epo 的总体反应。优化 ESA 作为癌症患者重要支持治疗方式的使用，并进一步研究 Epo-EpoR 在癌症生物学中的作用，需要结合精心设计的临床前和临床研究，旨在不仅确定 ESA 治疗对肿瘤反应、无进展和总生存等临床结果的影响，还要研究 Epo 对 EpoR 激活生物标志物以及与肿瘤生物学和放化疗反应相关的因素的潜在影响。
Erythropoiesis-stimulating agents (ESA) used for the treatment of chemotherapy-induced anemia in cancer patients have been associated with adverse outcomes of enhanced tumor progression and impaired survival in a series of recent clinical trials. As clinical practice guidelines for ESA administration in cancer patients have evolved to improve safety, the mechanisms underlying the adverse outcomes and whether ESAs exert direct and/or indirect effects in primary tumors to modulate tumor cell growth, survival, and chemoradiotherapy responses remain uncertain. Erythropoietin receptor (EpoR) expression in tumor cells has raised the simplistic possibility that Epo signaling mediated via a functional cellular receptor may contribute to tumor progression in a direct manner. However, Epo biology in cancer is likely to be complex and an interplay of multiple factors is potentially involved in the overall tumor response to exogenous Epo. Optimization of ESA use as an important supportive therapy modality in cancer patients, and further investigation of the role of Epo-EpoR in cancer biology will require a combination of carefully designed preclinical and clinical studies designed to ascertain not only the effect of ESA therapy on clinical outcomes such as tumor response, progression-free, and overall survival but also to investigate the potential effects of Epo on biomarkers of EpoR activation and factors related to tumor biology and chemoradiation responsiveness.