Clinical Pharmacology and Pharmacogenetics Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Clinical Oncology Unit 1, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.
Eur J Pharmacol. 2024 Apr 15;969:176424. doi: 10.1016/j.ejphar.2024.176424. Epub 2024 Feb 23.
The therapeutic landscape of estrogen receptor (ER)-positive breast cancer includes endocrine treatments with aromatase inhibitors (AIs), selective estrogen receptor modulators (SERMs), and selective estrogen receptor degraders (SERDs). Fulvestrant is the first approved SERD with proven efficacy and good tolerability in clinical practice. However, drug resistance, low receptor affinity, and parental administration stimulated the search for new oral SERDs opening a new therapeutic era in ER + breast cancer. Elacestrant is an orally bioavailable SERD that has been recently approved by the FDA for postmenopausal women with ER+, human epidermal growth factor receptor 2-negative (HER2-), estrogen receptor 1 (ESR1)-mutated advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy. Other molecules of the same class currently tested in clinical trials are amcenestrant, giredestrant, camizestrant, and imlunestrant. The current review article offers a detailed pharmacological perspective of this emerging drug class, which may help with their possible future clinical applications.
雌激素受体 (ER) 阳性乳腺癌的治疗方法包括使用芳香化酶抑制剂 (AIs)、选择性雌激素受体调节剂 (SERMs) 和选择性雌激素受体降解剂 (SERDs) 的内分泌治疗。氟维司群是首个获批的 SERD，在临床实践中已被证明具有疗效和良好的耐受性。然而，耐药性、低受体亲和力和母体给药促使人们寻找新的口服 SERD，从而为 ER+乳腺癌开辟了一个新的治疗时代。Elacestrant 是一种口服生物利用的 SERD，最近被 FDA 批准用于绝经后妇女的 ER+、人表皮生长因子受体 2 阴性 (HER2-)、雌激素受体 1 (ESR1) 突变的晚期或转移性乳腺癌，这些患者在内分泌治疗至少一线治疗后疾病进展。目前正在临床试验中测试的其他同类药物包括 amcenestrant、giredestrant、camizestrant 和 imlunestrant。本文详细介绍了这一新兴药物类别的药理学观点，这可能有助于其未来的临床应用。
