Novel targets for VEGF-independent anti-angiogenic drugs.

INTRODUCTION: In the last decades, the active research in the field of tumor angiogenesis led to the development of a class of agents providing an effective inhibition of neovessels formation through the blockade of VEGF-related pathways. More recently, the identification of several non-VEGF factors such as PDGF, FGF, HGF, angiopoietins, ALK1/endoglin, endothelis and ephrins involved in tumor angiogenesis have emphasized the need to develop agents targeting multiple pro-angiogenic pathways. AREAS COVERED: This review aimed at summarizing the role of non-VEGF molecular pathways in targeting tumor angiogenesis. Preclinical and clinical data for investigational agents against non-VEGF targets have been reviewed emphasizing the role of combined inhibition strategies. EXPERT OPINION: Besides the successful development of drugs providing a specific VEGF blockade, novel agents targeting alternative angiogenesis-related pathways are being tested. Although it seems that the potential clinical usefulness of these novel compounds have been not yet fully investigated, sunitinib, sorafenib, pazopanib and other multikinase inhibitors have certainly displayed encouraging results. A more in-depth clarification of anti-angiogenic agents is still needed, in order to design the best clinical setting and schedule for target-based agents and possibly anticipate potential tools to overcome the emerging issue of anti-angiogenic drug resistance.