Review article Molecular Origins of Cancer

The current era of research in antiangiogenic therapy for cancer began in earnest in 1971 with the publication of Folkman’s imagina-tive hypothesis,1 but 33 years would elapse before the first drug developed as an inhibitor of angiogenesis was approved by the Food and Drug Administration (FDA).2,3 This approval was based on the survival benefit observed in a randomized phase 3 trial of first-line treatment of metastatic colorectal cancer; in that trial, bevacizumab, a humanized monoclonal antibody directed against vascular endo-thelial growth factor (VEGF), was combined with conventional chemotherapy.4 Bevacizumab therapy also increased overall survival in the first-line treatment of advanced non–small-cell lung cancer when used in combination with standard chemotherapy.5 Two other antiangiogenic drugs, sorafenib and sunitinib, have also been approved by the FDA; these are oral small-molecule-receptor tyrosine kinase inhibitors (RTKIs). They target multiple receptor tyrosine kinases, including VEGF receptors and platelet-derived growth factor (PDGF) receptors.6 Sorafenib and suni-tinib have been beneficial in the treatment of metastatic renal-cell cancer when used alone.7,8 Sorafenib monotherapy is also active in the treatment of hepatocel-lular carcinoma9 and was recently approved by the FDA for this indication