ALK: a tyrosine kinase target for cancer therapy.
ALK: a tyrosine kinase target for cancer therapy.
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DOI：
10.1101/mcs.a001115
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发表时间：
2017-01
影响因子：
1.8
通讯作者：
Simon GR
中科院分区：
文献类型：
--
作者：
Holla VR;Elamin YY;Bailey AM;Johnson AM;Litzenburger BC;Khotskaya YB;Sanchez NS;Zeng J;Shufean MA;Shaw KR;Mendelsohn J;Mills GB;Meric-Bernstam F;Simon GR
间变性淋巴瘤激酶（ALK）基因在脑发育中起重要的生理作用，并且在几种恶性肿瘤中可能发生致癌性改变，包括非小细胞肺癌（NSCLC）和间变性大细胞淋巴瘤（ALCL）。最常见的ALK改变是导致融合基因的染色体重排，如在ALCL和NSCLC中所见。在其他肿瘤中，已经描述了ALK拷贝数增加和激活ALK突变。当接受ALK抑制剂治疗时，在ALK改变患者中观察到显著且通常延长的应答。其中三种药物-克唑替尼、塞瑞替尼和阿来替尼-现已被FDA批准用于治疗ALK融合阳性的转移性NSCLC。然而，抵抗的出现是普遍的。正在开发更新的ALK抑制剂和其他靶向策略，以抵消ALK抑制剂耐药的新出现机制。这篇综述概述了我们对ALK改变的肿瘤的理解和治疗的最新进展。
The anaplastic lymphoma kinase (ALK) gene plays an important physiologic role in the development of the brain and can be oncogenically altered in several malignancies, including non-small-cell lung cancer (NSCLC) and anaplastic large cell lymphomas (ALCL). Most prevalent ALK alterations are chromosomal rearrangements resulting in fusion genes, as seen in ALCL and NSCLC. In other tumors, ALK copy-number gains and activating ALK mutations have been described. Dramatic and often prolonged responses are seen in patients with ALK alterations when treated with ALK inhibitors. Three of these—crizotinib, ceritinib, and alectinib—are now FDA approved for the treatment of metastatic NSCLC positive for ALK fusions. However, the emergence of resistance is universal. Newer ALK inhibitors and other targeting strategies are being developed to counteract the newly emergent mechanism(s) of ALK inhibitor resistance. This review outlines the recent developments in our understanding and treatment of tumors with ALK alterations.