TGF-beta in cancer and as a therapeutic target.

Cancer develops through a series of genetic changes leading to malignant transformation. Numerous gene and pathways involved in stages of progression to frank malignancy have been elucidated. These genetic changes result in aberrations in fundamental cellular processes controlling proliferation, apoptosis, differentiation and genomic stability. Metastasis is the hallmark of malignancy. The process of metastasis is extremely complex and involves steps including dissemination of tumor cells from the primary tumor through the vascular and lymphatic system and growth selectively in distant tissues and organs. Transforming growth factor-beta which is a growth suppressive cytokine in many normal situations becomes an active and important participant in malignant disease including angiogenesis, extracellular matrix deposition, immuno-suppression and metastasis growth promotion. Transforming growth factor-beta and its receptors are targets for antibody therapeutics and small molecule kinase inhibitors.