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雌激素与雌激素受体(ER)介导的信号转导途径在乳腺癌的发生发展中起着至关重要的作用。内分泌治疗是ER阳性乳腺癌患者全身治疗的重要方法,通过阻断ER途径抑制肿瘤细胞的生长。近年来,非甾体抗雌激素类药物的应用是内分泌治疗的一个重要进展。他莫昔芬(TAM)是常用的抗雌激素药物,已广泛应用于临床,有较好的疗效。但是,肿瘤细胞对TAM的原发性和获得性耐受限制了其在临床上的应用。近期研究强调,生长因子受体和其他信号激酶途径高度激活,可介导ER基因组和非基因组作用,导致TAM治疗耐受。体外实验和临床研究证实,EGFR/HER2途径在TAM内分泌治疗耐受中的作用更为显著,提示阻断其信号转导途径有可能克服TAM耐受。
Estrogen and estrogen receptor (ER) -mediated signaling pathways play a crucial role in the development of breast cancer. Endocrine therapy is an important method of systemic therapy in patients with ER-positive breast cancer, and inhibits the growth of tumor cells by blocking the ER pathway. In recent years, the application of non-steroidal anti-estrogen drugs is an important progress of endocrine therapy. Tamoxifen (TAM) is a commonly used anti-estrogen drug that has been widely used in clinical practice and has good efficacy. However, the primary and acquired tolerance of TAM to tumor cells limits its clinical application. Recent studies have highlighted that highly-activated growth factor receptors and other signaling pathways can mediate genomic and non-genomic ER, leading to TAM treatment tolerance. In vitro experiments and clinical studies have confirmed that EGFR / HER2 pathway plays a more significant role in the endocrine therapy tolerance of TAM, suggesting that it is possible to overcome TAM tolerance by blocking its signal transduction pathway.