选择性雌激素受体（ER）降解剂（SERD）富维司汀因口服生物利用度低而在乳腺癌（BC）治疗中的使用受到限制。口服生物利用度良好的探索性SERD elacestrant与富维司汀的比较显示，两种药物均影响携带多种ESR1突变的ER+患者来源异种移植瘤模型的肿瘤生长，但elacestrant在耐受富维司汀后仍然有效。在内分泌敏感和耐药乳腺癌细胞系模型中，两种药物均对ER-cistrome、ER-interactome和雌激素调节基因的转录产生相似的影响，证实了elacestrant的抗雌激素活性。将elacestrant与CDK4/6抑制剂联合使用可增强抗增殖效果，相较于单一疗法。此外，elacestrant可抑制palbociclib耐药细胞的生长。最后，elacestrant耐药涉及可治疗靶点的I型和II型受体酪氨酸激酶。我们的数据支持对elacestrant进行更广泛的临床测试。©2022年，作者（们）。

The selective oestrogen receptor (ER) degrader (SERD), fulvestrant, is limited in its use for the treatment of breast cancer (BC) by its poor oral bioavailability. Comparison of the orally bioavailable investigational SERD elacestrant, versus fulvestrant, demonstrates both drugs impact tumour growth of ER+ patient-derived xenograft models harbouring several ESR1 mutations but that elacestrant is active after acquired resistance to fulvestrant. In cell line models of endocrine sensitive and resistant breast cancer both drugs impact the ER-cistrome, ER-interactome and transcription of oestrogen-regulated genes similarly, confirming the anti-oestrogenic activity of elacestrant. The addition of elacestrant to CDK4/6 inhibitors enhances the antiproliferative effect compared to monotherapy. Furthermore, elacestrant inhibits the growth of palbociclib-resistant cells. Lastly, resistance to elacestrant involves Type-I and Type-II receptor tyrosine kinases which are amenable to therapeutic targeting. Our data support the wider clinical testing of elacestrant.© 2022. The Author(s).