Abstract
The approval of the first kinase inhibitor, Gleevec, ushered in a paradigm shift for oncological treatment—the use of genomic data for targeted, efficacious therapies. Since then, over 48 additional small-molecule kinase inhibitors have been approved, solidifying the case for kinases as a highly druggable and attractive target class. Despite the role deregulated kinase activity plays in cancer, only 8% of the kinome has been effectively “drugged.” Moreover, 24% of the 634 human kinases are understudied. We have developed a comprehensive scoring system that utilizes differential gene expression, pathological parameters, overall survival, and mutational hotspot analysis to rank and prioritize clinically relevant kinases across 17 solid tumor cancers from The Cancer Genome Atlas. We have developed the clinical kinase index (CKI) app (http://cki.ccs.miami.edu) to facilitate interactive analysis of all kinases in each cancer. Collectively, we report that understudied kinases have potential clinical value as biomarkers or drug targets that warrant further study.
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CKI is a novel method to prioritize dark kinases as cancer drug targetsExpression of understudied kinases in tumors is prognostic of poor outcomesDark kinases are likely clinically relevant cancer targetsCancer cell dependency correlates with tumor pathology and survival
Essegian et. al conduct a kinome-wide pan-cancer analysis and provide an intuitive interface to prioritize understudied kinases as prospective novel cancer drug targets. While many of the approved kinase drug targets rank high in each cancer cohort, several understudied kinases also appear to be clinically relevant and warrant further exploration.
