Inhibitors of the Hedgehog Signal Transduction Pathway

Aberrant Hedgehog (Hh) signaling plays an important role in the pathogenesis and maintenance of many cancers. The mechanisms by which this pathway contributes to tumor progression are only now being unraveled. There appear to be two distinct ways by which Hh signaling becomes constitutively activated in tumors: by over expression of the ligand itself, or by acquisition of mutations in Hh signaling components at or downstream of the Hh receptor. The goal of this review is to briefly present the key components of the Hh pathway, and then discuss the known inhibitors of this pathway. We will describe how each inhibitor was identified, what is known of its mechanism of action, and its potential as a therapeutic agent against tumors dependent on Hh signaling.