Journal
DRUG RESISTANCE UPDATES
Volume 12, Issue 3, Pages 74-80Publisher
CHURCHILL LIVINGSTONE
DOI: 10.1016/j.drup.2009.03.002
Keywords
Angiogenesis; VEGF; Hypoxia; HIF-1; Bevacizumab; Cancer therapeutics; Topotecan; mTOR inhibitors
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Funding
- National Institutes of Health [N01-CO-12400]
- National Cancer Institute
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Angiogenesis, a key process for the growth of human cancers, has recently been exploited for the development of a novel class of cancer therapeutics that was thought to have wide applications and not to induce resistance in the clinical setting. Indeed, anti-angiogenic therapy has become an important option for the management of several human malignancies. However, a significant number of patients either do not respond to anti-angiogenic agents or fairly rapidly develop resistance. In addition, the benefit of anti-angiogenic therapy is relatively short-lived and the majority of patients eventually relapses and progresses. Several mechanisms of resistance to anti-angiogenic therapy have been recently proposed. The current review focuses on the role of intra-tumor hypoxia as a mechanism of resistance to anti-angiogenic agents and speculates on therapeutic approaches that might circumvent resistance and thereby improve clinical outcome. (C) 2009 Elsevier Ltd. All rights reserved.
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