The Hedgehog Signaling Pathway in Cancer

Abstract

The Hedgehog (Hh) signaling pathway plays crucial roles during embryonic development, where it controls cell proliferation, differentiation, and tissue patterning in numerous tissues and organs (Ingham and McMahon 2001; Cohen 2003). Mutations in genes encoding key members of the pathway can result in many human developmental disorders, including defects of the CNS, craniofacial, limb, and skeletal disorders. After embryogenesis, the overall activity of the pathway is diminished. However, recent reports demonstrate the necessity for Hh signaling in proliferation and maintenance of stem cell-like progenitor cells in the adult (Altaba et al. 2004). Interestingly, Hh signaling has also been implicated in the genesis and growth of a variety of human tumors (Pasca and Hebrok 2003), thus creating links between embryonic development, stem cell maintenance, and cancer formation. Several studies have shown reduced growth of tumor cells in response to inhibition of Hh signaling, suggesting a value for inhibiting pathway activity in a clinical setting. Elements of the Hh signaling pathway may thus represent potential drug targets for the treatment of a subset of cancers. This chapter provides an overview of the Hh signaling pathway and reviews the role of Hh signaling in tumor formation and growth. The potential role of Hh antagonists in cancer treatment is also reviewed and discussed.