Activating Mutations in ERBB2 and Their Impact on Diagnostics and Treatment.
Activating Mutations in ERBB2 and Their Impact on Diagnostics and Treatment.
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DOI：
10.3389/fonc.2013.00086
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发表时间：
2013
影响因子：
4.7
通讯作者：
Wong KK
中科院分区：
文献类型：
--
作者：
Herter-Sprie GS;Greulich H;Wong KK
尽管正在进行“抗癌战争”，但癌症仍然是人类发病率和死亡率的主要原因之一。一种新的靶向治疗模式对未来最有希望，这使得识别肿瘤特异性治疗靶点至关重要。ERBB 2/HER 2，最为人所知的是它在乳腺癌肿瘤发生中的作用，可以通过两种类型的药理学操作来靶向：针对细胞外受体结构域的抗体治疗和针对细胞内酪氨酸激酶结构域的小分子化合物。基因扩增导致的ERBB 2异常激活已被证明参与乳腺、卵巢、胃、结肠直肠、肺、脑和头颈部肿瘤的病理生理学。然而，下一代测序技术的出现使得能够有效地鉴定ERBB 2的激活分子改变。在这篇综述中，我们将集中在这些体细胞突变，导致ERBB 2受体激活的功能作用。我们还将讨论目前针对突变激活ERBB 2的临床前和临床治疗策略。
Despite the ongoing “war on cancer,” cancer remains one of the major causes of human morbidity and mortality. A new paradigm of targeted therapies holds the most promise for the future, making identification of tumor-specific therapeutic targets of prime importance. ERBB2/HER2, best known for its role in breast cancer tumorigenesis, can be targeted by two types of pharmacological manipulation: antibody therapy against the extracellular receptor domain and small molecule compounds against the intracellular tyrosine kinase domain. Aberrant activation of ERBB2 by gene amplification has been shown to participate in the pathophysiology of breast, ovarian, gastric, colorectal, lung, brain, and head and neck tumors. However, the advent of next-generation sequencing technologies has enabled efficient identification of activating molecular alterations of ERBB2. In this review, we will focus on the functional role of these somatic mutations that cause ERBB2 receptor activation. We will additionally discuss the current preclinical and clinical therapeutic strategies for targeting mutationally activated ERBB2.