DisABLing imatinib

Mutations in BCR-ABL tyrosine kinase have long been associated with resistance to Gleevec imatinib, but they only account for about half of all cases. University of Massachusetts researchers have shown that upregulation of protein kinase Ch could be an alternative cause and might provide a new target for bypassing resistance.¹ But blocking the downstream signaling components could be easier than creating specific inhibitors of the relatively unexplored protein kinase C isoform.

In the study, the team showed that upregulation of protein kinase Ch (PRKCH; PKCh) enhances activity of the RAF/MEK/ERK pathway in models of imatinib-resistant chronic myelogenous leukemia (CML) that did not involve BCR-ABL tyrosine kinase mutations...