Department of Pharmaceutical Sciences and Natural Products, Central University of Punjab, Ghudda, Bathinda (Pb), 151401, India.
Curr Med Chem. 2023;30(29):3287-3314. doi: 10.2174/0929867329666221006110528.
Breast cancer is considered to be 2most common cancer subtype investigated worldwide. It is mainly prevalent in postmenopausal women. Estrogen Receptor (ER) is a primary transcription factor for the survival and growth of tumors. Around 80% BCs of all classes are ER-positive (ER+). Powerful evidence for estrogen proved to be involved in BC pathogenesis both exogenously and endogenously. It brings the concept of ER inhibitors to treat BC with distinct mechanisms into focus and ER PROTACs (Proteolysis-Targeting Chimeras), AIs (Aromatase inhibitors), SERMs (Selective estrogen receptor modulators), and SERDs (Selective estrogen receptor degrader) were developed. For over 30 years, Tamoxifen, a triphenylethylene SERM, was the drug of choice solely to treat ER+BC patients. Although several SERMs got approval by US FDA after tamoxifen, complicacies remain because of dangerous adverse effects like endometrial carcinoma, hot flashes, and VTE (Venous thromboembolism). In addition to that, drug-resistant tumors put a surging need for novel, potent candidates with no or low adverse effects for ER+ BC prevention.
This article explores the possibilities of SERMs as effective BC agents.
A detailed literature survey of the history and recent advancements of SERMs has been carried out, taking BC as the primary target. This review provides information about ER structure, signaling, pharmacological action, chemical classification with SAR analysis, and benefits and adverse effects of SERMs as potential BC agents.
Exhaustive literature studies suggested that SERMs having an agonistic, antagonistic or mixed activity to ER could efficiently inhibit BC cell proliferation.
Each chemical class of SERMs comprises some salient features and potentials, which may be further investigated to obtain novel effective SERMs in BC therapy.
乳腺癌被认为是全球研究最多的第二常见癌症亚型。它主要发生在绝经后妇女中。雌激素受体（ER）是肿瘤生存和生长的主要转录因子。大约 80%的所有类别乳腺癌都是 ER 阳性（ER+）。强有力的证据表明，雌激素无论是外源性还是内源性，都参与了乳腺癌的发病机制。这将 ER 抑制剂的概念引入到治疗乳腺癌的独特机制中，并开发了 ER PROTACs（蛋白水解靶向嵌合体）、AIs（芳香酶抑制剂）、SERMs（选择性雌激素受体调节剂）和 SERDs（选择性雌激素受体降解剂）。30 多年来，三苯乙烯 SERM 他莫昔芬一直是唯一用于治疗 ER+乳腺癌患者的药物。尽管在他莫昔芬之后，几种 SERMs 获得了美国 FDA 的批准，但由于子宫内膜癌、热潮红和 VTE（静脉血栓栓塞）等危险的不良反应仍然存在并发症。此外，耐药肿瘤的出现迫切需要新型、有效且不良反应低的候选药物来预防 ER+乳腺癌。
本文探讨了 SERMs 作为有效乳腺癌治疗药物的可能性。
对 SERMs 的历史和最新进展进行了详细的文献调查，主要以乳腺癌为研究对象。本综述提供了有关 ER 结构、信号转导、药理学作用、化学分类与 SAR 分析以及 SERMs 作为潜在乳腺癌治疗药物的益处和不良反应的信息。
详尽的文献研究表明，具有激动剂、拮抗剂或混合活性的 SERMs 可以有效抑制乳腺癌细胞的增殖。
每一类 SERMs 都具有一些显著的特点和潜力，可以进一步研究以获得治疗乳腺癌的新型有效 SERMs。
