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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.

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Non-small-cell lung cancers: a heterogeneous set of diseases

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The emerging complexity of gene fusions in cancer

TL;DR: The spectrum of gene fusions in cancer and how the methods to identify them have evolved are described, and the conceptual implications of current, sequencing-based approaches for detection are discussed.
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Erratum: Non-small-cell lung cancers: a heterogeneous set of diseases

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The landscape and therapeutic relevance of cancer-associated transcript fusions.

TL;DR: The landscape of transcript fusions detected across a large number of tumor samples was described and revealed fusion events with clinical relevance that have not been previously recognized, support the concept of basket clinical trials and reveal an important role for tumorigenesis.
References
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Journal ArticleDOI

Acquired Resistance to Crizotinib from a Mutation in CD74–ROS1

TL;DR: A biopsy of a resistant tumor was performed and an acquired mutation leading to a glycine-to-arginine substitution at codon 2032 in the ROS1 kinase domain was identified, suggesting that this mutation was an early event in the clonal evolution of resistance.
Journal Article

Pattern of radiation-induced RET and NTRK1 rearrangements in 191 post-chernobyl papillary thyroid carcinomas: biological, phenotypic, and clinical implications.

TL;DR: The genotype/phenotype evaluation of post-Chernobyl PTCs reveals a characteristic spectrum of gene rearrangements that lead to typical phenotypes with important biological and clinical implications.
Journal ArticleDOI

Oncogenic FGFR3 gene fusions in bladder cancer

TL;DR: As urothelial cell lines with FGFR3 fusions are extremely sensitive to FGFR-selective agents, the presence of a fusion gene may aid in selection of patients forFGFR-targeted therapy.
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