Genetic instability is one of the hallmarks of cancer cells. As tumors grow, they progressively acquire mutations that ultimately allow them to invade normal tissues and metastasize to distant sites. This increased propensity for mutation also leads to cancers that are resistant to therapeutic intervention. Recent evidence has shown that the tumor microenvironment plays a major role in the etiology of this phenomenon; as tumors are exposed to repeated cycles of hypoxia and reoxygenation, they downregulate a number of DNA repair pathways, thus leading to genetic instability. Understanding the mechanisms involved in this process may provide insights into the development of novel treatment strategies.
Copyright © 2010 Elsevier Inc. All rights reserved.