The hedgehog (Hh) cell signaling pathway promotes cell growth and differentiation during embryonic development. Hh signaling is frequently aberrantly activated in cancer. The Hh signaling pathway may be activated by hedgehog ligands (sonic, desert, indian) binding to PTCH1 on the cell surface. In the absence of a hedgehog ligand, the Hh pathway is inhibited by PTCH1. PTCH1 inhibits the activation of SMO by maintaining SMO inside a vesicle within the cell. 
Figure 1. In the absence of hedgehog ligands, patched (PTCH1) is an inhibitory receptor that inhibits hedgehog signaling by maintaining the activating receptor smoothened (SMO) within a vesicle inside the cell. The binding of hedgehog ligands (sonic, desert, and indian) bind to PTCH1 releases PTCH1 from SMO and causes PTCH1 to be internalized and degraded. SMO migrates to the cell surface and initiates hedgehog signaling. The activation of SMO causes gene transcription and promotes normal embryonic development as well as cell growth and survival. Specific nodes in the pathway that are therapeutically actionable are noted.
SMO is the most frequent biomarker that serves as an inclusion criterion in therapies targeting the hedgehog signaling pathway.
Biomarkers in the hedgehog signaling pathway serve as inclusion eligibility criteria in 14 clinical trials, of which 11 are open and 3 are closed. The genes PTCH1, SMO, and SUFU on this pathway most frequently harbor alterations that are inclusion eligibility criteria for clinical trials.
Of the trials that contain alteration(s) in the hedgehog signaling pathway as inclusion criteria, 4 are phase 1 (3 open), 2 are phase 1/phase 2 (2 open), 7 are phase 2 (5 open), and 1 is phase 4 (1 open) .