ALK gene rearrangements: a new therapeutic target in a molecularly defined subset of non-small cell lung cancer.

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摘要：

Transforming rearrangements of theALK(anaplastic lymphoma kinase) gene have recently been described in non-small cell lung cancer (NSCLC). The most common rearrangement arises from an inversion in the short arm of chromosome 2 that creates a fusion between the 5′ portion of theEML4(echinoderm microtubule-associated protein-like 4) gene and the 3′ portion of theALKgene. At least sevenALKgene rearrangement variants have been described involving differentEML4-ALKbreakpoints or rarely other non-EML4fusion partners.ALKrearrangements may be readily identified in tumor tissue by reverse transcription-polymerase chain reaction or fluorescent in situ hybridization. AlthoughALKgene rearrangements affect only about 4% of all lung cancers, they are more frequent in adenocarcinomas, in never or light smokers, and seem almost mutually exclusive with activatingEGFRorKRASmutations. Promising results seen in patients with NSCLC containing fluorescent in situ hybridization-detectedALKrearrangements treated on a phase I study with PF02341066, an oral ALK inhibitor, indicate thatALKrepresents a new therapeutic target in this molecularly defined subset of NSCLC.

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关键词：

ALK Lung cancer

DOI：

10.1097/JTO.0b013e3181c4dedb

被引量：

367

年份：

2009