Angiogenesis is necessary for
tumor growth.
Drug discovery efforts have identified several potential therapeutic targets on endothelial cells and selective inhibitors capable of slowing
tumor growth or producing
tumor regression by blocking angiogenesis in in vivo
tumor models. Certain antiangiogenic
therapeutics increase the activity of cytotoxic anticancer treatments in preclinical models. More than 75 antiangiogenic compounds have entered clinical trials. Most of the early clinical testing was conducted in patients with advanced disease resistant to standard
therapies. Several phase III trials have been undertaken to compare the efficacy of standard
chemotherapy versus the same in combination with an experimental
angiogenesis inhibitor. Preliminary results of the clinical studies suggest that single-
agent antiangiogenic therapy is poorly active in advanced
tumors. Although some of the results of combination trials are controversial, recent positive outcomes with an antivascular
endothelial growth factor antibody combined with
chemotherapy as front-line
therapy of metastatic
colorectal cancer have renewed enthusiasm for this therapeutic strategy. This article presents an overview of experimental and clinical studies of combined
therapy with
antiangiogenic agents and highlights the challenges related to the appropriate strategies for selection of the patients, study design, and choice of proper end points for preclinical and clinical studies using these agents.