Investigation into Ligand-Dependent Hedgehog Signalling in Development and Cancer

The Hedgehog (Hh) signalling pathway plays critical roles in both developmental processes and cancer. However, the mechanisms known to regulate Hh signalling in cancer are not well understood. Investigating Hh signalling in models of development and cancer revealed a novel interaction between the cancer-related genes, p53 and Rb, and the cell-surface structure required for Hh signalling, primary cilia. Targeting this association with Hh-inhibitor drugs led to increased survival and tumour shrinkage in mouse models of the paediatric bone cancer, osteosarcoma. These findings propose p53 and Rb mutations, and primary cilia frequency as predictive biomarkers for Hh-inhibitor therapy in cancer.