The Cardinal Edge


The Hedgehog (Hh) signaling pathway is a developmental pathway that is highly conserved evolutionarily. While typically only displaying high activity during embryogenesis, overactivation of the Hh pathway in adults has been linked to multiple forms of cancer including acute myeloid leukemia, myelofibrosis, basal-cell carcinoma, pancreatic ductal adrenal carcinoma, and triple negative breast cancer. The prevalence of Hh activation in many different cancers has made it a prime target for inhibition of these cancers through novel therapies. This literature review sought to assess the current state of cancer treatment through inhibition of Hh signaling. Most current clinical trials involving the pathway use Smoothened (SMO) antagonists to limit GLI1 production and ultimately inhibit Hh signaling. Currently, the FDA has approved the use of the SMO antagonists vismodegib, sonidegib, and glasdegib for cancer treatment. While only these small molecule inhibitors of Hh signaling have been approved for cancer treatment at this point, inhibition of the Hh signaling has shown to be a promising avenue for novel cancer therapies, particularly for future treatment of basal-cell carcinoma.