Tyrosine kinase gene rearrangements in epithelial malignancies
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TLDR
The clinical outcomes with targeted therapies, aetiologic, pathogenic and clinical features that are associated with cancers harbouring oncogenic fusion kinases, including anaplastic lymphoma kinase (ALK), ROS1 and RET are examined.Abstract:
In this Review, the authors examine the aetiological, pathogenic and clinical features that are associated with cancers harbouring oncogenic fusion kinases, the clinical outcomes with targeted therapies, and strategies to discover additional kinases that are activated by chromosomal rearrangements in solid tumours. 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.read more
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TL;DR: Crizotinib is superior to standard chemotherapy in patients with previously treated, advanced non-small-cell lung cancer with ALK rearrangement and greater improvement in global quality of life with crizotinIB than with chemotherapy.
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