86 Cancer Drugs Mapped Against 758 Kinases Opens New Repurposing Possibilities
A landmark screen of approved kinase inhibitors reveals 94% of cancer mutations are already targetable — and uncovers surprising new drug uses.
Summary
Researchers at Fred Hutchinson Cancer Center systematically tested 86 approved kinase-blocking drugs against 758 kinase proteins — including hundreds of cancer-causing mutant variants. The study dramatically expanded the number of kinases that can be targeted by existing drugs, from 89 to 235. Crucially, 94% of known cancer-driving mutations and 97% of gene fusions in the dataset were inhibited by at least one already-approved drug. The team also validated several unexpected drug-target pairings: one lung cancer drug showed promise against pancreatic cancer, another against glioblastoma, and a third could overcome drug resistance in certain tumors. A free web tool called KIRHub was released so clinicians and researchers can explore the full dataset to guide precision cancer treatment decisions.
Detailed Summary
Protein kinases — enzymes that regulate nearly every aspect of cell signaling — are among the most important drug targets in cancer medicine. Over 100 kinase inhibitors have now been approved by regulators, yet most were developed for narrow indications. A major question in oncology is whether these drugs could be repurposed to treat cancers driven by different but related mutations.
To answer this, researchers at Fred Hutchinson Cancer Center and Reaction Biology conducted the most comprehensive biochemical profiling of approved kinase inhibitors to date. They tested 86 of the roughly 100 approved kinase inhibitors against a panel of 758 kinases — including 409 wild-type (normal) kinases and 349 oncogenic (cancer-causing) variants, spanning point mutations and gene fusions.
The results were striking. The number of kinases considered druggable by existing approved drugs jumped from 89 to 235 — more than doubling the therapeutic landscape. Ninety-four percent of the cancer-driving mutations and 97% of the gene fusions in the dataset were inhibited by at least one existing approved drug, suggesting that many patients with rare or treatment-resistant mutations may already have a viable therapeutic option.
The team experimentally validated several repurposing discoveries. Tepotinib, approved for lung cancer, was found to target the IRAK1/4-cholesterol pathway in glioblastoma. Brigatinib, another lung cancer drug, showed activity against the MARK2/3-Hippo pathway in pancreatic cancer. Gilteritinib, used in leukemia, demonstrated the ability to overcome MET mutation-driven drug resistance and metastasis.
To make these findings actionable, the researchers released KIRHub, a free web-based tool allowing clinicians and scientists to query wild-type and mutant kinase inhibitor data. Caveats include that biochemical assays do not fully replicate cellular or in vivo conditions, and clinical validation of repurposing candidates will require further trials.
Key Findings
- Druggable kinases expanded from 89 to 235 using only already-approved drugs.
- 94% of cancer-driving mutations are inhibited by at least one existing approved drug.
- Tepotinib shows new activity against IRAK1/4-cholesterol pathway in glioblastoma.
- Brigatinib targets MARK2/3-Hippo pathway, suggesting utility in pancreatic cancer.
- Gilteritinib can overcome MET mutation-driven drug resistance and tumor metastasis.
Methodology
The study used a biochemical kinase assay to profile 86 approved kinase inhibitors against 758 kinases, including 409 wild-type and 349 oncogenic variants (point mutations and fusions). Key repurposing findings were experimentally validated in relevant cancer models. A companion web tool, KIRHub, was developed to enable open exploration of the full dataset.
Study Limitations
This summary is based on the abstract only, as the full paper is not open access. Biochemical kinase assays measure direct binding and inhibition but do not capture cellular pharmacokinetics, off-target toxicity, or in vivo efficacy. Repurposing candidates identified here will require clinical validation before patient use.
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