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lüll Role of the hypoxic tumor microenvironment in the resistance to anti-angiogenic therapies Rapisarda A; Melillo GDrug Resist Updat 2009[Jun]; 12 (3): 74-80Angiogenesis, 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.|Angiogenesis Inhibitors/*pharmacology/therapeutic use[MESH]|Cell Hypoxia/*drug effects/*physiology[MESH]|Combined Modality Therapy[MESH]|Drug Resistance, Neoplasm/*physiology[MESH]|Humans[MESH]|Neoplasms/*blood supply/drug therapy/*physiopathology[MESH]|Neovascularization, Pathologic/drug therapy/*physiopathology[MESH] |