Development of selective casein kinase 1 delta/epsilon inhibitors for cancer

Casein kinase 1 (CK1) is a key component of both canonical and non-canonical Wnt pathways, which were shown to drive chronic lymphocytic leukemia (CLL) by several mechanisms (Wang et al., 2014, Kaucka et al., 2013). Also other types of cancer, such as breast, prostate cancer or others were previously shown to depend on Wnt/CK1 activity and the pathway inhibition was suggested as a potential form of therapy. In recent study, we showed that CK1 inhibition can block processes involved in CLL progression in vitro as well as in vivo in the Eµ-TCL1 mouse model of CLL (Janovska et al., 2018). Importantly, CK1 inhibition showed synergistic effects with ibrutinib treatment in blocking chemotaxis of CLL cells, a process important for CLL pathogenesis and showed to be beneficial also in vivo.