title: The role of hypoxia in cancer progression, angiogenesis, metastasis, and resistance to therapy.
abstract: Hypoxia is a non-physiological level of oxygen tension, a phenomenon common in a majority of malignant tumors. Tumor-hypoxia leads to advanced but dysfunctional vascularization and acquisition of epithelial-to-mesenchymal transition phenotype resulting in cell mobility and metastasis. Hypoxia alters cancer cell metabolism and contributes to therapy resistance by inducing cell quiescence. Hypoxia stimulates a complex cell signaling network in cancer cells, including the HIF, PI3K, MAPK, and NFĸB pathways, which interact with each other causing positive and negative feedback loops and enhancing or diminishing hypoxic effects. This review provides background knowledge on the role of tumor hypoxia and the role of the HIF cell signaling involved in tumor blood vessel formation, metastasis, and development of the resistance to therapy. Better understanding of the role of hypoxia in cancer progression will open new windows for the discovery of new therapeutics targeting hypoxic tumor cells and hypoxic microenvironment.
authors: Department of Radiation Oncology, Cancer Biology Division, Washington University School of Medicine in St Louis, MO, USA.
authors: Barbara
authors: B
authors: Muz
authors: Department of Radiation Oncology, Cancer Biology Division, Washington University School of Medicine in St Louis, MO, USA.
authors: Pilar
authors: P
authors: de la Puente
authors: Department of Radiation Oncology, Cancer Biology Division, Washington University School of Medicine in St Louis, MO, USA.
authors: Feda
authors: F
authors: Azab
authors: Department of Radiation Oncology, Cancer Biology Division, Washington University School of Medicine in St Louis, MO, USA.
authors: Abdel Kareem
authors: AK
authors: Azab
keywords: angiogenesis; cancer; hypoxia; metastasis; treatment resistance