Nass Norbert, Kalinski Thomas
Department of Pathology, Otto von Guericke University Magdeburg, Leipziger Str. 44, D 39120 Magdeburg, Germany.
Department of Pathology, Otto von Guericke University Magdeburg, Leipziger Str. 44, D 39120 Magdeburg, Germany.
Pathol Res Pract. 2015 Mar;211(3):189-97. doi: 10.1016/j.prp.2015.01.004. Epub 2015 Jan 21.
Tamoxifen is still the most frequently used antiestrogen for the treatment of patients with premenopausal, estrogen receptor positive breast cancer. However, in 20-30% of these cases, tamoxifen therapy fails due to an existing or developing resistance. The prediction of tamoxifen resistance by appropriate biomarker analysis and the development of novel therapies for tamoxifen resistance in premenopausal breast cancer is, therefore, an important goal of ongoing research. Tamoxifen resistance is associated with altered estrogen receptor expression especially on the plasma membrane, including the alternative G-protein coupled receptor GPR-30 (GPER) and estrogen receptor splice products, such as ERα36. Tamoxifen resistant cells often use alternative pathways to promote proliferation in the absence of genomic estrogen signaling. These pathways involve the epidermal growth factor EGF, the inflammation associated transcription factor NF-κB- and the IGF-1 pathway. Tamoxifen resistant mamma carcinoma cell lines are useful models to understand tamoxifen resistance in-vitro and to search for prognostic or predictive biomarkers. Furthermore, such cell lines can be used to identify potential targets for therapy.
他莫昔芬仍然是治疗绝经前雌激素受体阳性乳腺癌患者最常用的抗雌激素药物。然而，在这些病例中，有20%-30%的患者由于存在或产生耐药性，他莫昔芬治疗失败。因此，通过适当的生物标志物分析预测他莫昔芬耐药性以及开发针对绝经前乳腺癌他莫昔芬耐药的新疗法，是正在进行的研究的一个重要目标。他莫昔芬耐药与雌激素受体表达改变有关，尤其是在质膜上，包括替代性G蛋白偶联受体GPR-30（GPER）和雌激素受体剪接产物，如ERα36。他莫昔芬耐药细胞在缺乏基因组雌激素信号的情况下，常利用替代途径促进增殖。这些途径涉及表皮生长因子EGF、炎症相关转录因子NF-κB和IGF-1途径。他莫昔芬耐药的乳腺癌细胞系是了解体外他莫昔芬耐药性以及寻找预后或预测生物标志物的有用模型。此外，此类细胞系可用于识别潜在的治疗靶点。
