Antiangiogenic agents and gastrointestinal cancers

The role of angiogenesis in tumor development and the identification of VEGF as a key factor in this process have recently led to the development of anti-angiogenic agents in the treatment of cancer. Among them, the major are those targeting the VEGF pathway, including anti-VEGF antibodies (bevacizumab) and VEGF receptor tyrosine kinase inhibitors (vatalanib, sorafenib, sunitinib...). Other therapeutic strategies inhibiting angiogenesis are under investigation, targeting the VEGF pathway or other crucial steps of angiogenesis. In digestive oncology, bevacizumab was the first anti-angiogenic agent to be registered in the fist-line treatment of metastatic colorectal cancer in which it was proved to be efficient in combination with a 5-fluorouracile (5FU)/acide folinique (AF) with or without irinotecan-based chemotherapy. Sunitinib and sorafenib have more recently been shown to be active in gastrointestinal stromal tumors and advanced hepatocellular carcinoma, respectively. Side effects associated with these anti-angiogenic agents are not those usually observed with conventional anticancer drugs and require a specific management. Many anti-angiogenic agents are currently under investigation in digestive tumors, opening new prospects but also raising many questions. (c) 2008 Elsevier Masson SAS. Tous droits reserves.