Angiogenesis and Lymphangiogenesis: New Molecular Targets for the Treatment of Cancer and Inflammation

Abstract

In order to grow beyond minimal size, tumors need to induce the growth of new blood vessels (angiogenesis), and systemic blockade of angiogenesis has been recently approved for the treatment of select types of human cancers. We identified the natural angiogenesis inhibitors thrombospondin-1 (TSP-1) and TSP-2 as potent inhibitors of ultraviolet light-induced skin damage and of cancer formation and metastasis, leading to new molecular approaches for chemoprevention. We also established the new concept of active tumor lymphangiogenesis, and we identified tumor lymphangiogenesis as a novel prognostic indicator for metastasis and patient survival of human cancers. We discovered VEGF as a major pathogenetic factor in chronic inflammation and established anti-angiogenic therapy as a novel strategy to treat inflammatory diseases. The overall goals of our ongoing research are to identify and to characterize molecular targets controlling inflammatory and tumor angiogenesis and lymphangiogenesis, using genetic disease models together with genomics approaches and chemical library screens, and to characterize genetic polymorphisms to determine disease susceptibility and to develop individualized therapeutic strategies.