Novel Inhibitors targeting oncogenic Hedgehog/GLI signaling

Targeted inhibition of the Hedgehog/GLI signalling pathway has shown impressive therapeutic effects in selected cancers. However, many patients develop resistance to Hedgehog inhibitors at baseline or during the course of therapy, making the evaluation of novel, innovative compounds as Hedgehog inhibitors of great clinical relevance. In this project, the effects of two novel compounds on Hedgehog/GLI signalling will be investigated, IC50 values measured and compared with clinically approved inhibitors. Experiments will include in vitro studies with human cancer cell lines and analytical approaches to measure mRNA and protein expression of selected Hedgehog target genes. Compounds will be compared and evaluated for inhibitory activity in Hedgehog-dependent and Hedgehog-independent cell models.