Tumor angiogenesis and molecular targets for therapy.

Tumors produce multiple angiogenic factors to induce neovascularization by angiogenesis, vasculogenesis and vascular remodeling. Although tumors utilize similar mechanisms as normal growing tissues, tumor blood vessels usually appear as malformed vasculatures that have several distinctive features including a high degree of disorganization, lack of clear separation between arterioles and venules, lack of appropriate coating with mural cells, high permeability, and composition of mosaic cell types, which might express specific markers. These unusual features of tumor blood vessels offer a great opportunity for therapeutic intervention and might paradoxically restrict cytotoxic drug delivery. Following an initial clinical success of bevacizumab in combination with chemotherapy for the treatment of human colorectal cancer, several other anti-angiogenesis agents are now available in the clinic. Understanding basic mechanisms of tumor angiogenesis, defining novel and accurate molecular targets, designing optimal clinical trials, and minimizing side effects are crucial issues for a further successful development of anti-angiogenic compounds for the treatment of various human cancers.