Research ArticleCancer

A precision therapy against cancers driven by KIT/PDGFRA mutations

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Science Translational Medicine  01 Nov 2017:
Vol. 9, Issue 414, eaao1690
DOI: 10.1126/scitranslmed.aao1690

Treatment makes tumors feel BLU

Mutations in receptor tyrosine kinases are common in cancer, and a variety of kinase mutations can have oncogenic effects. Not all of these mutations are susceptible to existing kinase inhibitors, and many inhibitors are nonspecific, resulting in undesirable off-target effects. Evans et al. developed BLU-285, an inhibitor that specifically targets the KIT and PDGFRA oncogenic kinases. The authors showed that the compound is very specific for its targets, can inhibit them in the presence of multiple oncogenic mutations, and is selective for the mutant forms of the kinases relative to the wild type. In addition to biochemical and preclinical testing of BLU-285, the authors conducted a phase 1 study, which showed evidence of the compound’s activity in human cancer patients.