Comprehensive profiling of clinically approved kinase inhibitors reveals mutation-specific inhibitors and opportunities for drug repurposing

In the human body, proteins called kinases act as biological control switches, directing how cells grow, divide, and survive. When these switches get stuck in the "on" position due to genetic mutations, they can drive the uncontrolled cell growth seen in cancer. Over the past two decades, scientists have developed dozens of drugs called kinase inhibitors to block these faulty switches. Typically, these medications are designed to target one specific broken protein, but scientists have long suspected they might be able to block other targets as well.

A massive new study has put that idea to the test. Researchers evaluated 92 clinical kinase inhibitors against a staggering 758 different kinase variations, including both normal and mutated versions. Their findings dramatically expanded the known capabilities of these existing medications, revealing that the number of targetable kinases jumps from 89 to 235. Even more remarkably, 94 percent of the mutated kinases and 97 percent of the fused genes they tested could be blocked by at least one currently approved drug.

The research team also experimentally validated several promising new uses for these existing medications. For example, they found that a drug called tepotinib could potentially be repurposed to fight glioblastoma, a severe brain tumor, while another drug called brigatinib showed promise against pancreatic cancer. To help doctors and researchers explore this data, the team launched a free online database called KiRHub to match genetic mutations with existing drugs.