Itraconazole in Non Small Cell Lung Cancer

Circulating levels of angiogenic factors have been correlated with aggressive tumor growth, prediction of metastasis and prognosis in a wide range of solid tumors, including non-small cell lung cancer. Food and Drug Administration (FDA) approved Itraconazole as an anti-angiogenic agent including both Vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF), and inhibited phosphorylation of the primary angiogenic receptors for these factors in 2007 and also known as an inhibitor of Hedgehog signalling, AKT (protein kinase B)/mechanistic target of rapamycin (mTOR) signaling adding its induction of autophagic cell death function based on cellular and laboratory studies, and allowed its use in phase II trials in prostate, lung and skin cancer. Itraconazole also interferes directly with mitochondrial Adenosine triphosphate (ATP) production, leading to the activation of the adenosine monophosphate (AMP) -activated protein kinase pathway and subsequent inhibition of mTOR pathway (Head et al., 2015). Testing Itraconazole on experimental settings was associated also with tumor hypoxia, as proved by induction of tumor-specific expression of Hypoxia-inducible factor 1-alpha (HIF1α), as well as decreased tumor micro-vessel load