A Screening Method for the ALK Fusion Gene in NSCLC.
A Screening Method for the ALK Fusion Gene in NSCLC.
复制标题
NSCLC中ALK融合基因的筛选方法。
DOI：
10.3389/fonc.2012.00024
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发表时间：
2012
影响因子：
4.7
通讯作者：
Yatabe Y
中科院分区：
文献类型：
--
作者：
Murakami Y;Mitsudomi T;Yatabe Y
近年来，肺癌的研究在了解肺癌的分子发病机制和开发肺癌的治疗方法方面取得了重大进展。这些成果直接用于临床实践。事实上，棘皮微管相关蛋白样间变性淋巴瘤激酶(ALK)融合基因于2007年首次在非小细胞肺癌中被描述，并于2011年批准了一种针对这种融合的分子靶向药物。然而，ALK融合的肺癌只占肺癌的一小部分；因此，有效的患者选择是使用ALK抑制剂成功治疗的关键。目前检测ALK融合的常用方法有RT-PCR、荧光原位杂交(FISH)和免疫组织化学等。尽管FISH是目前的黄金标准技术，但还没有完美的方法来检测这些基因变化。在这篇文章中，我们讨论了每种方法的优缺点以及选择更有可能发生ALK融合的患者的可能标准。如果我们能够成功地筛查患者，那么ALK抑制剂治疗将是个性化治疗的最佳例子，因为它可以从具有相同肿瘤表型的较大组中选择具有不常见基因的患者。换句话说，个性化治疗可能会给当前的临床肿瘤学带来新的挑战。
Lung cancer research has recently made significant progress in understanding the molecular pathogenesis of lung cancer and in developing treatments for it. Such achievements are directly utilized in clinical practice. Indeed, the echinoderm microtubule-associated protein-like 4–anaplastic lymphoma kinase (ALK) fusion gene was first described in non-small cell lung cancer in 2007, and a molecularly targeted drug against the fusion was approved in 2011. However, lung cancer with the ALK fusion constitutes only a small fraction of lung cancers; therefore, efficient patient selection is crucial for successful treatment using the ALK inhibitor. Currently, RT-PCR, fluorescent in situ hybridization (FISH), and immunohistochemistry are commonly used to detect the ALK fusion. Although FISH is currently the gold standard technique, there are no perfect methods for detecting these genetic alterations. In this article, we discuss the advantages and disadvantages of each method and the possible criteria for selecting patients who are more likely to have the ALK fusion. If we can successfully screen patients, then ALK inhibitor treatment will be the best example of personalized therapy in terms of selecting patients with an uncommon genotype from a larger group with the same tumor phenotype. In other words, the personalized therapy may offer a new challenge for current clinical oncology.