Hedgehog pathway inhibitors: Potential applications in breast cancer

The Hedgehog (Hh) signaling pathway is a developmental pathway with important roles in embryogenesis, epithelial-mesenchymal transition, stem/progenitor cell renewal, and tissue regeneration and repair. Dysregulated Hh signaling is implicated in 25% of human cancers, including breast cancer. Mutations within elements of the Hh signaling pathway leading to ligand-independent activation do not appear to be widespread in breast cancer. However, overexpression of the Hh ligand and Hh target genes has been reported in breast cancer, suggesting a ligand-dependent mechanism for Hh pathway activation in breast carcinogenesis. Small molecule antagonists of the Hh pathway are under clinical development and may present novel therapeutic options for breast cancer.