Research ArticleCancer therapy

Differential abundance of CK1α provides selectivity for pharmacological CK1α activators to target WNT-dependent tumors

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Sci. Signal.  27 Jun 2017:
Vol. 10, Issue 485, eaak9916
DOI: 10.1126/scisignal.aak9916

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Treating WNT-driven tumors

The WNT signaling pathway powers the growth of various tumors, particularly colorectal cancer (CRC). However, WNT-targeted inhibitors are very toxic to normal gastrointestinal tissue, precluding their approval for clinical use. Li et al. show that WNT could be targeted by activating a kinase that inhibits the pathway. A small-molecule activator of the kinase CK1α called SSTC3 suppressed WNT activity in CRC cell lines, prevented tumor growth, and increased survival in mouse models of primary and metastatic CRC. Because the effects of SSTC3 were selective to cells with high WNT activity and low CK1α abundance, SSTC3 was minimally toxic to normal gastrointestinal epithelium. Thus, SSTC3 and its future derivatives may be a promising therapeutic for CRC patients.