Importance of hypoxia in tumor progression: road to Nobel price and novel therapeutic opportunities

SUMMARY – It is now evident that cancer hypoxia is one of the new hallmark of cancer due to its consequences in gene expression, metabolism and biology. The importance of cancer hypoxia was recognized by the Nobel-price award in 2019. There are three major causes of cancer hypoxia: insuffi cient vascularization, systemic hypoxia of the host and constitutive activation of oncogene driven signaling pathways, all leading to a unique form of genetic reprogramming by HIF transcription factors. The consequences of HIF activation in cancer is the angiogenic phenotype, a new metabolic profi le and an immunsuppressive microenvironment. Furthermore, cancer hypoxia and the cellular adaptation lead to therapy resistance. Accordingly there is an urgent need to develop target therapies of hypoxia to improve effi cacies of various therapeutic modalities.