乳腺癌内分泌治疗耐药相关机制的研究进展

摘要

内分泌治疗作为雌激素受体（estrogen receptor，ER）阳性乳腺癌的主要治疗方案被广泛应用。他莫西芬（tamoxifen，Tam）是乳腺癌内分泌治疗最常用的药物，它通过与雌激素竞争性结合ERα来降低雌激素的生物学活性，抑制细胞的增殖，从而治疗乳腺癌。然而，肿瘤细胞所表现出的原发性或获得性的他莫西芬耐药使得其临床应用受到了限制，寻找克服他莫西芬耐药的治疗策略已经刻不容缓。目前为止，他莫西芬耐药的相关机制已部分明确，但仍需进一步研究。有证据表明ERα、生长因子受体信号通路及microRNA的表达异常等多种机制均与他莫西芬耐药有关。本文对他莫西芬耐药的相关机制进行了具体分析，以期为ER阳性乳腺癌的治疗提供新思路。%Endocrine therapy is widely accepted to treat ER positive breast cancer patients.Tamoxifen is the most commonly used endocrine therapy in breast cancer,which can competitively bind to estrogen receptor and inhibit the cell proliferation.However,both primary and acquired resistance to tamoxifen limit its widespread clinical applicat-ions.So,it's extremely urgent to explore strategy to overcome tamoxifen resistance.At present,mechanisms contributing to tamoxifen resistance are still not fully understood.There is evidence showing that the interaction between ERαand growth factor receptor signaling pathways,and dys-regulated microRNAs play important roles during acquired resist-ance of tamoxifen.In this paper,we summarized relative mechanisms leading to tamoxifen resistance and provide new thoughts for ER positive breast cancer treatment.