Sonic the hedgehog is one of the most extraordinary video games
The HEDGEHOG Pathway
The body of the fruit fly is vertically segmented
Segmentation of the fly's body is due to the "hedgehog genes".
In vertebrates, there are a few homologues of these. The key ligand is named Sonic hedgehog (SHH) after Sonic the Hedgehog,  the game released by SEGA (you can play by clicking here).
Four major cancer signaling pathways are known thanks to the fruit fly :
- Notch,
- DPP,
- Hedgehog
- and Wnt
In 1995, Eric Wieschaus, Edward B. Lewis and Christiane Nüsslein-Volhard were awarded the Nobel Prize in Medicine, for their work revealing the extraordinary complexity of the Hedgehog pathway.
The pathway is remarkably described in Wikipedia
SONIC HEDGEHOG (=SHH) is a protein we all have
SHH binds to Patched 1, a membrane receptor, and stops it from inhibiting SMO
SMO activates carcinogenic transcription factors in the nucleus
PTCH1 is mutated in basal cell carcinoma (BCC)
Vismodegib is a small therapeutic molecule which binds to SMO (smoothened)
It is active in BCC, medulloblastoma, and in xenograft models of colorectal and pancreatic cancer
PF 04449913, and Novartis molecules LDE 225 and LEQ 506 also inhibit SMO, and are also in clinical trials (2012)
These factors induce substances that transform normal cells into cancer cells
non inhibited SMO...
...goes to the nucleus