乳腺癌内分泌治疗耐药机制研究进展

内分泌治疗(ednocrine therapy,ET)是乳腺癌综合治疗中的重要措施之一,选择性雌激素受体调节剂(selectiveestrogen receptor modulators,SERMs)、第三代芳香化酶抑制剂(aromatase inhibi-tors,AIs)和氟维司群是重要的内分泌治疗药物。但目前内分泌疗法面临的最大难题是原、继发耐药,其确切机制尚不清楚,近年来的研究发现,多种因素与耐药相关,如ER信号传导途径中的共激活与共抑制因子的比例,HER-2生长因子受体的高表达,各生长因子和激酶的串话调节,雌激素受体基因关键氨基酸位点的突变和多态、芳香化酶基因的突变与多态以及他莫昔芬(tamoxifen,TAM)代谢异常等。

Progress of research on drug-resistance mechanisms of endocrine therapy in breast cancer

Endocrine therapy is one of the most important therapeutics in breast cancer systemic therapy. Selective estrogen receptor modulators, the third-generation aromatase inhibitors and fulvestrant are all crucial endocrine therapeutic drugs. However, the most puzzling problem of endocrine therapy is the primary and acquired drug resistance, moreover, the drug resistance mechanisms has not been fully understood. There are many factors significantly associated with drug resistance, such as the ratio of coactivators and corepressors in estrogen receptor (ER) signalling pathway, the high expression of human epidermal growth factor receptor (HER)-2, cross-talk between the estrogen receptor (ER) signalling pathway and various growth factors or intracellular kinase, mutations and polymorphisms of critical amino acid in ER gene, mutations and polymorphisms of aromatase gene, abnormal metablism of tamoxifen and so on.