Oncogenic kinase fusions: an evolving arena with innovative clinical opportunities

Fabrizio Tabbò; Marco Pizzi; Peter W. Kyriakides; Bruce Ruggeri; Giorgio Inghirami

doi:10.18632/oncotarget.7853

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Oncogenic kinase fusions: an evolving arena with innovative clinical opportunities

Fabrizio Tabbò, Marco Pizzi, Peter W. Kyriakides, Bruce Ruggeri and Giorgio Inghirami _

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Oncotarget. 2016; 7:25064-25086. https://doi.org/10.18632/oncotarget.7853

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Abstract

Fabrizio Tabbò1,2, Marco Pizzi2,3, Peter W. Kyriakides2, Bruce Ruggeri4 and Giorgio Inghirami1,2,5

1 Department of Molecular Biotechnology and Health Science and Center for Experimental Research and Medical Studies (CeRMS), University of Torino, Torino, Italy

2 Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY, USA

3 General Pathology and Cytopathology Unit, Department of Medicine-DIMED, University of Padova, Padova, Italy

4 Pre-Clinical Discovery Biology, Incyte Corporation, Wilmington, DE, USA

5 Department of Pathology, and NYU Cancer Center, New York University School of Medicine, New York, NY, USA

Correspondence to:

Giorgio Inghirami, email:

Keywords: tyrosine kinase fusions, translocations, signaling pathways, small molecule inhibitors, resistance mechanisms

Received: October 14, 2015 Accepted: January 24, 2016 Published: March 02, 2016

Abstract

Cancer biology relies on intrinsic and extrinsic deregulated pathways, involving a plethora of intra-cellular and extra-cellular components. Tyrosine kinases are frequently deregulated genes, whose aberrant expression is often caused by major cytogenetic events (e.g. chromosomal translocations). The resulting tyrosine kinase fusions (TKFs) prompt the activation of oncogenic pathways, determining the biological and clinical features of the associated tumors. First reported half a century ago, oncogenic TKFs are now found in a large series of hematologic and solid tumors. The molecular basis of TKFs has been thoroughly investigated and tailored therapies against recurrent TKFs have recently been developed. This review illustrates the biology of oncogenic TKFs and their role in solid as well as hematological malignancies. We also address the therapeutic implications of TKFs and the many open issues concerning their clinical impact.

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Oncogenic kinase fusions: an evolving arena with innovative clinical opportunities

Abstract