Bachmann-Moisson N, Barberi-Heyob M, Merlin J L
Laboratoire de recherche en oncologie, Centre Alexis-Vautrin, Vandoeuvre-les-Nancy, France.
Bull Cancer. 1997 Jan;84(1):69-75.
Tamoxifen is the most currently used antiestrogen in the endocrine treatment of breast cancer. However, despite a small proportion of estrogen receptor positive tumors presenting de novo resistance to treatment, numerous tumors develop acquired resistance after a first phase of response. Many mechanisms have been proposed, but none could be identified as a real explanation of these phenomena of resistance. The hypotheses suggested are related to the series of events implied in the transduction of the signal following the ligand binding to estrogen receptor and concerning several levels: (1) loss or mutation of the estrogen receptor; (2) modification in estrogen receptor associated parameters; (3) alteration in the estrogen response element; (4) high levels of antiestrogen binding sites; (5) alteration of metabolism or availability of tamoxifen. The tamoxifen resistance certainly concerns several of these mechanism. Therefore, it is necessary to go on studying these mechanisms and to elucidate the connections existing between all of them.
他莫昔芬是目前乳腺癌内分泌治疗中使用最广泛的抗雌激素药物。然而，尽管一小部分雌激素受体阳性肿瘤对治疗呈现出原发性耐药，但许多肿瘤在第一阶段反应后会产生获得性耐药。人们提出了许多机制，但没有一种能被确定为这些耐药现象的真正解释。所提出的假说是与配体与雌激素受体结合后信号转导中所涉及的一系列事件相关的，涉及几个层面：（1）雌激素受体的缺失或突变；（2）雌激素受体相关参数的改变；（3）雌激素反应元件的改变；（4）抗雌激素结合位点水平高；（5）他莫昔芬代谢或可用性的改变。他莫昔芬耐药肯定涉及这些机制中的几种。因此，有必要继续研究这些机制，并阐明它们之间存在的联系。
