The hypoxic tumor microenvironment: driving the tumorigenesis of non-small-cell lung cancer

Since the application of molecular biology in cancer biology, lung cancer research has classically focused on molecular drivers of disease. One such pathway, the hypoxic response pathway, is activated by reduced local oxygen concentrations at the tumor site. Hypoxia-driven gene and protein changes enhance epithelial-to-mesenchymal transition, remodel the extracellular matrix, drive drug resistance, support cancer stem cells and aid evasion from immune cells. However, it is not the tumor cells alone which drive this response to hypoxia, but rather their interaction with a complex milieu of supporting cells. This review will focus on recent advances in our understanding of how these cells contribute to the tumor response to hypoxia in non-small-cell lung cancer.