title: Mechanisms of resistance to anti-angiogenesis therapies.
abstract: Angiogenesis, the formation of new blood vessels from preexisting ones, provides oxygen and nutrients to actively proliferating tumor cells. Hence, it represents a critical aspect of tumor progression and metastasis. Because inhibition of angiogenesis represents a major approach to cancer treatment, the development of inhibitors of angiogenesis is a major challenge. The first FDA approved anti-angiogenic drug bevacizumab, a humanized monoclonal antibody directed against the Vascular Endothelial Growth Factor (VEGF), has been approved for the treatment of metastatic colorectal, lung, breast, and kidney cancers. The encouraging results have lead to the development, in the past few years, of other agents targeting angiogenic pathways as potent anti-cancer drugs and a number of them have been approved for metastatic breast, lung, kidney, and central nervous system cancers. Despite a statistically significant increase in progression free survival, which has accelerated FDA approval, no major benefit to overall survival was described and patients inevitably relapsed due to acquired resistance. However, while progression free survival was increased by only a few months for the majority of the patients, some clearly benefited from the treatment with a real increase in life span. The objective of this review is to present an overview of the different treatments targeting angiogenesis, their efficacy and the mechanisms of resistance that have been identified in different cancer types. It is essential to understand how resistance (primary or acquired over time) develops and how it may be overcome.
authors.affiliation: University of Nice Sophia Antipolis, Institute for Research on Cancer and Aging of Nice (IRCAN) CNRS Unit 7284/INSERM Unit 1081, 33 Avenue de Valombrose, 06189 Nice, France.
authors.forename: Sandy
authors.initials: S
authors.lastname: Giuliano
authors.forename: Gilles
authors.initials: G
authors.lastname: Pagès
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*
chemical_list: D020533:Angiogenesis Inhibitors