HH INHIBITION WITH ITRACONAZOLE

PTCH inhibits SMO in the absence of Hedgehog ligand in normal tissue

Hh ligand binding to PTCH releases SMO and Gli1 is expressed, and cancer develops

Itraconazole (IT) binds to smoothened (SMO) to inhibit activation of the Gli-1 pathway which leads to the formation of cancerous tumors

PTCH is mutated in BCCNS and does not inhibit SMO which leads to Gli1 expression (BCC)

Itraconazole binds to SMO and prevents activation of the Gli1 pathway which causes BCC tumors