Gross Mitchell E, Jo Solomon, Agus David B
Louis Warschaw Prostate Cancer Center, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Clin Adv Hematol Oncol. 2004 Jan;2(1):53-6, 64.
The human epidermal growth factor receptor (HER) family of receptor tyrosine kinases is part of a network of pathways that are involved in the development and progression of prostate cancer. HER-kinase receptors include epidermal growth factor receptor (EGFR), HER2, HER3, and HER4, which must combine as dimers to affect signaling. Different combinations of receptors produce different qualities and levels of pathway activation. Among HER-family receptors, HER2 activation is particularly important in breast cancer, as HER2 gene amplification is associated with a distinct clinical course and response to treatment with a HER2-directed therapy (trastuzumab). Although HER2 can be over-expressed in prostate cancer, there is no clinical data to support the use of trastuzumab for prostate cancer patients. Preclinical and clinical data show that the activation of the HER-kinase axis is important for the progression of prostate cancer to androgen-independent disease. Data points towards the importance of inhibiting multiple members of the HER-kinase family to achieve more complete blockade of this axis for cancers other than HER2-overexpressing breast cancer. Multiple pharmaceutical agents that block the HER-kinase axis are currently being tested for patients with prostate cancer. These include antibodies, tyrosine kinase inhibitors, and novel strategies which seek to decrease HER2 expression.
人表皮生长因子受体（HER）酪氨酸激酶家族是参与前列腺癌发生和发展的信号通路网络的一部分。HER激酶受体包括表皮生长因子受体（EGFR）、HER2、HER3和HER4，它们必须以二聚体形式结合才能影响信号传导。不同的受体组合会产生不同性质和水平的信号通路激活。在HER家族受体中，HER2激活在乳腺癌中尤为重要，因为HER2基因扩增与独特的临床病程以及对HER2靶向治疗（曲妥珠单抗）的反应相关。尽管HER2在前列腺癌中可能过度表达，但尚无临床数据支持将曲妥珠单抗用于前列腺癌患者。临床前和临床数据表明，HER激酶轴的激活对于前列腺癌进展为去势抵抗性疾病很重要。数据表明，对于HER2过表达乳腺癌以外的癌症，抑制HER激酶家族的多个成员以更完全地阻断该轴很重要。目前正在对前列腺癌患者测试多种阻断HER激酶轴的药物。这些药物包括抗体、酪氨酸激酶抑制剂以及旨在降低HER2表达的新策略。
