TRANSFORMING GROWTH-FACTOR-BETA - PROSPECTS FOR CANCER PREVENTION AND TREATMENT

Transforming growth factor beta (TGF beta) has emerged as a pre-eminent negative growth factor with inhibitory effects on a range of malignant epithelial cell types. There is increasing evidence that the malignant phenotype is associated with an imbalance of growth factors within the local microenvironment of tissues. Oncogenic events promoting neoplastic progression could involve either an excess of positive growth factors or a deficiency of negative ones such as TGF beta. Whether altered levels of TGF beta are directly implicated in processes of carcinogenesis remains unresolved, but local endogenous levels of TGF beta can be manipulated pharmacologically. This may be of relevance to the mode of action of some agents with proven therapeutic efficacy. Thus, boosting of endogenous TGF beta levels could correct any pre-existing or acquired deficiency, or compensate for overproduction of positive stimulatory growth factors resulting from activation of cellular proto-oncogenes. This article reviews the evidence for modulation of TGF beta synthesis and production by several commonly used pharmacological agents, and assesses the clinical potential of this strategy both for the treatment of established tumours and prevention of malignancy.