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The role of hypoxia in cancer progression, angiogenesis, metastasis, and resistance to therapy

Authors Muz B, de la Puente P, Azab F, Azab AK

Received 30 July 2015

Accepted for publication 4 November 2015

Published 11 December 2015 Volume 2015:3 Pages 83—92

DOI https://doi.org/10.2147/HP.S93413

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Thomas Kietzmann

Peer reviewer comments 4

Editor who approved publication: Prof. Dr. Dörthe Katschinski


Barbara Muz, Pilar de la Puente, Feda Azab, Abdel Kareem Azab

Department of Radiation Oncology, Cancer Biology Division, Washington University School of Medicine in St Louis, MO, USA

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 NFκB 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.

Keywords: hypoxia, cancer, metastasis, angiogenesis, treatment resistance
 

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