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摘要
背景:乳腺癌被认为是全世界研究的第二大常见癌症亚型。它主要流行于绝经后妇女。雌激素受体 (ER) 是肿瘤存活和生长的主要转录因子。所有类别中大约 80% 的 BC 是 ER 阳性(ER)。强有力的证据表明,雌激素在外源性和内源性方面均参与了 BC 发病机制。它将 ER 抑制剂的概念引入了以不同机制治疗 BC 的焦点,并开发了 ER PROTAC(蛋白水解靶向嵌合体)、AI(芳香酶抑制剂)、SERM(选择性雌激素受体调节剂)和 SERD(选择性雌激素受体降解剂)。 30 多年来,三苯乙烯 SERM 的他莫昔芬一直是治疗 ER BC 患者的首选药物。尽管在他莫昔芬之后一些 SERM 获得了美国 FDA 的批准,但由于子宫内膜癌、潮热和 VTE(静脉血栓栓塞)等危险的副作用,并发症仍然存在。除此之外,耐药肿瘤对 ER BC 预防无副作用或副作用低的新型有效候选药物的需求激增。目标:本文探讨了 SERM 作为有效 BC 代理的可能性。 方法:对 SERM 的历史和最新进展进行了详细的文献调查,以 BC 为主要目标。本综述提供了有关 ER 结构、信号、药理作用、化学分类和 SAR 分析的信息,以及 SERM 作为潜在 BC 药物的益处和副作用。 结果:详尽的文献研究表明,对 ER 具有激动、拮抗或混合活性的 SERM 可有效抑制 BC 细胞增殖。 结论:每个化学类别的 SERM 都包含一些显着特征和潜力,可以进一步研究这些特征和潜力,以获得用于 BC 治疗的新型有效 SERM。
关键词: BC,ER,抑制剂,增殖,SAR,SERMs,他莫昔芬。
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