Importance of Aberrantly Activated Hedgehog/Gli Pathway in Tumour Progression

Cancer is the second most common cause of death in the Czech Republic. The treatment of this disease is very exhausting for the patients and the treatment has often limited success only. The disease often relapses after a period of remission. Moreover, metastases often appear in lungs, liver or other organs and worsen patients prognosis and probability of survival. The Hedgehog (Hh) signaling pathway is one of the important pathways that affects initiation and maintenance of various types of tumours. When aberrantly activated, Hh signaling pathway helps cells escape apoptosis, disturbs cell energy metabolism, influences the process of epithelial-mesenchymal transition, helps to escape immune system, maintains cancer stem cells and supports metastasis. The role of Hh signaling cascade in tumour initiation, maintenance and progression is intensively studied. Several types of inhibitors of this pathway were developed. The most intensively studied were inhibitors of the receptor Smoothened. Due to commonly occurring resistance, the research of other groups of inhibitors is in the centre of interest. These new drugs do not target receptor Smoothened but proteins standing downstream of Smoothened (inhibition of final Gli transcription factors). The drugs could give new hope to patients whose treatment fails.

This review summarizes the findings about the role of Hh signaling pathway in tumour development and describes the progress in the development of targeted inhibitors of this pathway.