The role of Hedgehog signaling in colorectal cancer

Colorectal cancer is the second deadliest cancer among adults and represents a major health burden with a high disease-related mortality of approximately 35%.⁹ There is a great need to improve the understanding of the molecular mechanisms that lead to tumor progression to predict which patients would benefit from which specific treatments.⁹

Analysis of human tumor tissue specimens has revealed the absence of mutations in components of the Hedgehog pathway but has demonstrated that colorectal tumors overexpress the Hedgehog ligand, Sonic Hedgehog.⁶ Overexpression of Hedgehog ligands in colorectal cancer may promote tumorigenesis. Epithelial tumor cells overexpressing Hedgehog ligands activate Hedgehog signaling in neighboring stromal cells. In turn, the stroma provides a favorable environment for tumor growth.³ Targeting the Hedgehog pathway in colorectal cancer may lead to less favorable tumor microenvironment conditions.