The Role of Erythropoietin and Erythropoiesis-Stimulating Agents in Tumor Progression
The Role of Erythropoietin and Erythropoiesis-Stimulating Agents in Tumor Progression
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DOI：
10.1158/1078-0432.ccr-10-2577
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发表时间：
2011-10-15
影响因子：
11.5
通讯作者：
Xenocostas, Anargyros
中科院分区：
文献类型：
--
作者：
Hedley, Benjamin D.;Allan, Alison L.;Xenocostas, Anargyros
在过去的几十年里，对促红细胞生成素（EPO）生理功能的理解有了显著的发展。EPO与促红细胞生成素受体（EPOR）结合，启动刺激生长、抑制细胞凋亡的信号传导，诱导红细胞祖细胞分化，增加红细胞质量。此外，EPO已被证明对多种组织发挥组织保护作用，表明其作用机制具有多效性。促红细胞生成剂（ESA）在临床上用于治疗癌症相关性贫血[化疗诱导贫血（CIA）]。最近的临床试验报告，在接受化疗的esa治疗的癌症患者中，不良事件增加和/或生存率降低，这可能与epo诱导的癌症进展有关。EPO/EPOR下游的信号通路已被证明影响正常细胞和肿瘤细胞的许多细胞功能，包括增殖、凋亡和耐药性。一些研究报道了对癌细胞增殖、化疗疗效降低、细胞凋亡减少和对选择性治疗的耐药性的影响，而另一些研究则显示无效。此外，针对特定信号通路的新的靶向癌症治疗可能会被esa拮抗。这种抗癌药物与esa触发的潜在生存信号之间的分子相互作用可能被低估了，并且可能导致某些试验中出现的生存降低。随着更多靶向抗癌疗法的出现，这些类型的相互作用可能会使肿瘤细胞获得耐药性，从而降低治疗效果。因此，更全面地了解所涉及的复杂途径将允许在肿瘤患者的CIA安全治疗中合理使用esa。临床癌症研究；17 (20);6373 - 80。(c) 2011年aacr。
Over the past few decades, understanding of the physiologic function of erythropoietin (EPO) has evolved significantly. EPO binds to erythropoietin receptors (EPOR), initiating signaling that stimulates growth, inhibits apoptosis, and induces the differentiation of erythroid progenitors to increase red blood cell mass. EPO has additionally been shown to exert tissue-protective effects on multiple tissues, suggesting a pleiotropic mechanism of action. Erythropoiesis-stimulating agents (ESA) are used clinically for treating cancer-related anemia [chemotherapy-induced anemia (CIA)]. Recent clinical trials have reported increased adverse events and/or reduced survival in ESA-treated cancer patients receiving chemotherapy, potentially related to EPO-induced cancer progression. Signaling pathways downstream of EPO/EPOR have been shown to influence numerous cellular functions in both normal and tumor cells, including proliferation, apoptosis, and drug resistance. Some studies have reported effects on proliferation, reduced chemotherapy efficacy, reduction of apoptosis, and resistance to selective therapies on cancer cell lines, whereas others have shown null effects. In addition, newer targeted cancer therapies that are directed toward specific signaling pathways may be antagonized by ESAs. This molecular interplay between anticancer agents and potential survival signals triggered by ESAs may have been underestimated and may contribute toward decreased survival seen in certain trials. As more targeted anticancer therapies become available, these types of interactions may mitigate therapeutic efficacy by allowing tumor cells to acquire drug resistance. Therefore, a more complete understanding of the complex pathways involved will allow for the rational use of ESAs for the safe treatment of CIA in oncology patients. Clin Cancer Res; 17(20); 6373-80. (C) 2011 AACR.