A role for estrogen receptor phosphorylation in the resistance to tamoxifen.
A role for estrogen receptor phosphorylation in the resistance to tamoxifen.
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DOI：
10.4061/2011/232435
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发表时间：
2011
影响因子：
1.9
通讯作者：
Michalides R
中科院分区：
文献类型：
--
作者：
de Leeuw R;Neefjes J;Michalides R
大约三分之二的人类乳腺癌病例是雌激素受体阳性的。这些患者的首选药物是他莫昔芬。然而，大约一半的原发性肿瘤切除后的复发是或成为耐药这种药物。虽然在实验室中已经确定了许多他莫昔芬耐药的机制，但目前只有少数已被转化为临床。本文着重介绍了雌激素受体不同位点上不同激酶的磷酸化在他莫昔芬耐药中的作用。我们将讨论参与ERα磷酸化的分子途径和激酶，以及它们如何影响他莫昔芬耐药性。最后，我们将详细阐述这些观察结果的临床转化以及在治疗开始前预测患者肿瘤样本中他莫昔芬反应的可能性。最初在实验室的发现可能会转化为使用一种古老而安全的抗癌药物：他莫昔芬对乳腺癌患者进行更好的个性化治疗。
About two thirds of all human breast cancer cases are estrogen receptor positive. The drug of first choice for these patients is tamoxifen. However, about half of the recurrences after removal of the primary tumor are or become resistant to this drug. While many mechanisms have been identified for tamoxifen resistance in the lab, at present only a few have been translated to the clinic. This paper highlights the role in tamoxifen resistance of phosphorylation by different kinases on different sites of the estrogen receptor. We will discuss the molecular pathways and kinases that are involved in phosphorylation of ERα and how these affect tamoxifen resistance. Finally, we will elaborate on the clinical translation of these observations and the possibility to predict tamoxifen responses in patient tumor samples before treatment onset. The findings made originally on the bench may translate into a better and personalized treatment of breast cancer patients using an old and safe anticancer drug: tamoxifen.