Instituto de Biologia Molecular y Celular del Cancer-CIC, Campus Miguel de Unamuno, 37007- Salamanca, Spain.
Curr Pharm Des. 2013;19(5):808-17. doi: 10.2174/138161213804547303.
Receptor tyrosine kinases play important roles in animal development and their deregulation has been linked to several pathologies, including cancer or diabetes. In cancer, the ERBB/HER family of receptors has been shown to participate in the pathophysiology of breast, gastric, colorectal, lung and head and neck tumors. Activation of HER receptors occurs by receptor-receptor interactions facilitated by ligand binding, overexpression or molecular alterations of the HER receptors. The best example is the known role of HER2 in the tumorigenesis of a proportion of breast tumors. In this review, we will describe the biological bases that govern HER receptor activation, and this will represent the bases for the explanation of how to target HER receptors in cancer. We will discuss the current therapeutic options to target HER receptors, which are based on anti-receptor antibodies or small molecule kinase inhibitors. We will also describe current clinical applications and future developments of agents which target HER receptors. Finally, we will mention mechanism of resistance to anti-HER therapies, and will describe options to overcome such resistances.
受体酪氨酸激酶在动物发育中发挥重要作用，其失调与多种病理学有关，包括癌症或糖尿病。在癌症中，已经表明 ERBB/HER 受体家族参与乳腺癌、胃癌、结直肠癌、肺癌和头颈部肿瘤的病理生理学。HER 受体的激活通过配体结合、HER 受体的过表达或分子改变促进的受体-受体相互作用发生。最好的例子是已知的 HER2 在一部分乳腺癌肿瘤发生中的作用。在这篇综述中，我们将描述控制 HER 受体激活的生物学基础，这将为解释如何在癌症中靶向 HER 受体提供基础。我们将讨论目前靶向 HER 受体的治疗选择，这些选择基于抗受体抗体或小分子激酶抑制剂。我们还将描述靶向 HER 受体的药物的当前临床应用和未来发展。最后，我们将提到抗 HER 治疗的耐药机制，并描述克服这些耐药性的选择。
