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非小细胞肺癌中 ALK 融合基因的筛查方法。

A Screening Method for the ALK Fusion Gene in NSCLC.

机构信息

Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Nagoya, Japan.

出版信息

Front Oncol. 2012 Mar 16;2:24. doi: 10.3389/fonc.2012.00024. eCollection 2012.

Abstract

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.

摘要

近年来,肺癌研究在理解肺癌的分子发病机制和开发治疗方法方面取得了重大进展。这些成就直接应用于临床实践。事实上,棘皮动物微管相关蛋白样 4-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描述,针对该融合的一种分子靶向药物于 2011 年获得批准。然而,具有 ALK 融合的肺癌仅占肺癌的一小部分;因此,使用 ALK 抑制剂成功治疗的关键是有效选择患者。目前,RT-PCR、荧光原位杂交(FISH)和免疫组织化学常用于检测 ALK 融合。虽然 FISH 目前是金标准技术,但没有完美的方法来检测这些遗传改变。本文讨论了每种方法的优缺点,以及选择更有可能具有 ALK 融合的患者的可能标准。如果我们能够成功筛选患者,那么 ALK 抑制剂治疗将是从具有相同肿瘤表型的更大患者群体中选择罕见基因型患者的个体化治疗的最佳范例。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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19f8/3356052/b78c77910579/fonc-02-00024-g001.jpg

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