Tyrosine kinase gene rearrangements in epithelial malignancies

被引:237
作者
Shaw, Alice T. [1 ]
Hsu, Peggy P. [1 ]
Awad, Mark M. [1 ]
Engelman, Jeffrey A. [1 ]
机构
[1] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA
基金
美国国家卫生研究院;
关键词
CELL LUNG-CANCER; PAPILLARY THYROID CARCINOMAS; ANAPLASTIC LYMPHOMA KINASE; RECURRENT CHROMOSOMAL TRANSLOCATIONS; ATOMIC-BOMB SURVIVORS; EML4-ALK FUSION GENE; PAN-FGFR INHIBITOR; RET PROTOONCOGENE; RET/PTC REARRANGEMENTS; GENOME INSTABILITY;
D O I
10.1038/nrc3612
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Chromosomal rearrangements that lead to oncogenic kinase activation are observed in many epithelial cancers. These cancers express activated fusion kinases that drive the initiation and progression of malignancy, and often have a considerable response to small-molecule kinase inhibitors, which validates these fusion kinases as 'druggable' targets. In this Review, we examine the aetiologic, pathogenic and clinical features that are associated with cancers harbouring oncogenic fusion kinases, including anaplastic lymphoma kinase (ALK), ROS1 and RET. We discuss the clinical outcomes with targeted therapies and explore strategies to discover additional kinases that are activated by chromosomal rearrangements in solid tumours.
引用
收藏
页码:772 / 787
页数:16
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