Combination of Antiangiogenic Therapy With Other Anticancer Therapies: Results, Challenges, and Open Questions

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 facto...