Inhibition of the hedgehog pathway for the treatment of cancer using Itraconazole

Abstract

Itraconazole (ITZ) is an anti-fungal drug that has been used in clinical practice for nearly 35 years. Recently, numerous experiments have shown that ITZ possesses anti-cancer properties. The Hedgehog (Hh) pathway plays a pivotal role in fundamental processes, including embryogenesis, structure, morphology and proliferation in various species. This pathway is typically silent in adult cells, and inappropriate activity is linked to various tumor types. The most important mechanism of ITZ in the treatment of cancer is inhibition of the Hh pathway through the inhibition of smoothened receptors (SMO), glioma-associated oncogene homologs (GLI), and their downstream targets. In this review, we discuss the mechanisms of ITZ in the treatment of cancer through inhibition of the Hh pathway, which includes anti-inflammation, prevention of tumor growth, induction of cell cycle arrest, induction of apoptosis and autophagy, prevention of angiogenesis, and drug resistance. We also discuss the clinical use of ITZ in many types of cancers. We hope this review will provide more information to support future studies on ITZ in the treatment of various cancers.