FDA approved inhibitors of oncogenic Hedgehog signaling have partially failed in clinical trials due to the development of drug resistance. These disappointing results urgently call for the identification of novel drug targets that overcome the problem of Hedgehog inhibitor resistance in human malignancies with high medical need.
The Aberger lab now reports on the identification of the kinase DYRK1B as novel target for the treatment of cancers with Hedgehog inhibitor resistance. Blocking DYRK1B function, either chemically or genetically, results in repression of oncogenic Hedgehog signaling by reducing the expression of GLI transcription factors. Further, the Aberger group together with the Munich based biotech company 4SC Discovery identified a novel DYRK1 inhibitor with therapeutic efficacy and pharmacological properties suitable for the use in future clinical trials. The results have been published in the latest edition of Oncotarget. Read the full study by Gruber et al.