Research ArticleCancer therapy

Developmental phosphoproteomics identifies the kinase CK2 as a driver of Hedgehog signaling and a therapeutic target in medulloblastoma

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Sci. Signal.  11 Sep 2018:
Vol. 11, Issue 547, eaau5147
DOI: 10.1126/scisignal.aau5147

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A targeted, resilient treatment for medulloblastoma

Medulloblastoma is an aggressive type of brain tumor that most often arises in children and lacks targeted therapeutic options. The subtypes driven by activity in the sonic hedgehog (SHH) pathway are particularly resistant to current drugs, such as those known as SMO inhibitors, which target this pathway. Purzner et al. used phosphoproteomics to track the development of mouse cells that give rise to medulloblastoma and identified the kinase CK2 as a likely target. CK2 inhibitors blocked the growth of SMO inhibitor–resistant, SHH-type human and mouse medulloblastoma cells and markedly extended the survival of tumor-bearing mice, in which the drug was well tolerated. One of the compounds also blocked the growth of tumors that had mutant CK2, suggesting that it is less susceptible to a common mode of drug resistance. A clinical trial is under way to test this inhibitor in pediatric patients.