TRANSFORMING GROWTH-FACTOR-BETA - PROSPECTS FOR CANCER PREVENTION ANDTREATMENT

Transforming growth factor beta (TGF beta) has emerged as a pre-eminen t negative growth factor with inhibitory effects on a range of maligna nt epithelial cell types. There is increasing evidence that the malign ant phenotype is associated with an imbalance of growth factors within the local microenvironment of tissues. Oncogenic events promoting neo plastic progression could involve either an excess of positive growth factors or a deficiency of negative ones such as TGF beta. Whether alt ered levels of TGF beta are directly implicated in processes of carcin ogenesis remains unresolved, but local endogenous levels of TGF beta c an be manipulated pharmacologically. This may be of relevance to the m ode of action of some agents with proven therapeutic efficacy. Thus, b oosting of endogenous TGF beta levels could correct any pre-existing o r acquired deficiency, or compensate for overproduction of positive st imulatory growth factors resulting from activation of cellular proto-o ncogenes. This article reviews the evidence for modulation of TGF beta synthesis and production by several commonly used pharmacological age nts, and assesses the clinical potential of this strategy both for the treatment of established tumours and prevention of malignancy.