CCS researchers led by the Aberger group in collaboration with 4SC biotech have identified the kinase CSNK1D as novel drug targets for the treatment of Hedgehog-inhibitor resistant cancers. The study by Peer et al. has been published in the latest issue of
Short summary: Uncontrolled activation of hedgehog (HH)—GLI signaling contributes to the development of several human malignancies. Targeted inhibition of the HH—GLI signaling cascade with small-molecule inhibitors can reduce cancer growth, but patient relapse is very common due to the development of drug resistance. Therefore, a high unmet medical need exists for new drug targets and inhibitors to achieve efficient and durable responses. In the current study, we identified CSNK1D as a novel drug target in the HH—GLI signaling pathway. Genetic and pharmacological inhibition of CSNK1D activity leads to suppression of oncogenic HH—GLI signaling, even in cancer cells in which already approved HH inhibitors are no longer effective due to resistance mechanisms. Inhibition of CSNK1D function reduces the malignant properties of so-called tumor-initiating cells, thereby limiting cancer growth and presumably metastasis. The results of this study form the basis for the development of efficient CSNK1D inhibitors for the therapy of HH—GLI-associated cancers.