IMR Press / FBL / Volume 15 / Issue 1 / DOI: 10.2741/3616

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article
The role of hypoxia and acidosis in promoting metastasis and resistance to chemotherapy
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1 Department of Medical Microbiology, Immunology, and Cell Biology, Southern Illinois University School of Medicine, PO Box 19629, Springfield, IL 62794, USA
2 Department of Pharmacology and SimmonsCooper Cancer Institute, Southern Illinois University School of Medicine, PO Box 19629, Springfield, IL 62794, USA
Academic Editor:Kounosuke Watabe
Front. Biosci. (Landmark Ed) 2010, 15(1), 213–225;
Published: 1 January 2010
(This article belongs to the Special Issue Pathogenesis of tumor progression in breast and prostate cancer)

By a multiplicity of mechanisms, hypoxia and acidosis create a nurturing environment for tumor progression and the evolution of metastatic, drug-resistant cells. Acidosis drives mutagenesis and promotes the subversion of checkpoints and apoptotic mechanisms. Hypoxic tissues secrete cytokines that undermine normal anti-tumor surveillance by macrophages, turning them into accomplices and facilitators of invasion and angiogenesis. Invasiveness is also abetted by acidosis, the result of shifting to an anaerobic glycolytic metabolism. These factors explain the generally poor prognosis indicated by tumors expressing hypoxia-inducible factor-1 (HIF-1). However, these insights into the physiology of hypoxic tumors have inspired the development of new chemotherapeutic approaches directed at these tissues, including bioreductive drugs and gene therapies, some of which are in clinical trials. The ability to target the hypoxic compartment should allow longer progression-free survival and overall survival of patients bearing solid tumor malignancies.

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