title: Role of the hypoxic tumor microenvironment in the resistance to anti-angiogenic therapies.
abstract: 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.
authors.affiliation: Tumor Hypoxia Laboratory - SAIC Frederick, Inc., NCI at Frederick, Frederick, MD 21702-1201, USA.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Rapisarda
authors.forename: Giovanni
authors.initials: G
authors.lastname: Melillo
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D015687:Cell Hypoxia / Q000187:drug effects* / Q000502:physiology*; D003131:Combined Modality Therapy; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D006801:Humans; D009369:Neoplasms / Q000098:blood supply* / Q000188:drug therapy / Q000503:physiopathology*; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000503:physiopathology*
chemical_list: D020533:Angiogenesis Inhibitors