The
TGF-beta pathway controls a broad range of cellular behavior including cell proliferation, differentiation, and apoptosis of various cell types including
tumor cells, endothelial cells, immune cells, and fibroblasts. Besides
TGF-beta's direct effects on
tumor growth and its involvement in neoangiogenesis have received recent attention. Germline mutations in
TGF-beta receptors or coreceptors causing Hereditary Hemorrhagic Teleangiectasia and the
Loeys-Dietz syndrome underline the involvement of
TGF-beta in vessel formation and maturation. Several therapeutic approaches are evaluated at present targeting the
TGF-beta pathway including utilization of
antisense oligonucleotides against
TGF-beta itself or
antibodies or small molecule inhibitors of
TGF-beta receptors. Some of these therapeutic agents have already entered the clinical arena including an antibody against the endothelium specific
TGF-beta class I receptor ALK-1 targeting
tumor vasculature. In conclusion, therapeutic manipulation of the
TGF-beta pathway opens great opportunities in future
cancer therapy.