CEP-1347 is a mixed lineage
kinase inhibitor tested in a large-scale phase 2/3 clinical trial in early
Parkinson's disease, in which its safety and tolerability, but nevertheless not efficacy, was demonstrated. Here we identify by
drug repositioning
CEP-1347 as a potential anti-cancer stem cell
drug. In vitro,
CEP-1347 efficiently induced differentiation and inhibited the self-renewal and
tumor-initiating capacities of human cancer stem cells from
glioblastoma as well as from pancreatic and
ovarian cancers at clinically-relevant concentrations, without impairing the viability of normal fibroblasts and neural stem cells. In vivo, a 10-day systemic administration of
CEP-1347 at a dose that was less than 1/10 the mouse equivalent of the dose safely given to humans for 2 years was sufficient to effectively reduce
tumor-initiating cancer stem cells within established
tumors in mice. Furthermore, the same treatment protocol significantly extended the survival of mice receiving orthotopic implantation of
glioma stem cells. Together, our findings suggest that
CEP-1347 is a promising candidate for cancer stem cell-targeting
therapy and that further clinical and preclinical studies are warranted to evaluate its efficacy in
cancer treatment.