Therapeutic implications of the TGF-beta system.

This review considers the various roles of the TGF-beta system in mammary carcinogenesis, tumor progression, and cellular responses to therapeutic measures. The paradigm that has evolved from the work of many investigators suggests that loss of tumor cell responsiveness to the effects of TGF-beta can result in a crucial shift in the net effect of TGF-beta within the context of the tumor-host interaction. Principal elements of host-tumor interactions in which this shift may play out, including immune suppression, angiogenesis, and modification of the surrounding extracellular matrix by tumor cells, are potentially amenable to manipulation. Additional effects of TGF-beta, such as suggested by reports of its ability to alter the drug resistance of tumor cells and the drug sensitivity of normal tissues, suggest that appropriate molecular intervention designed to affect the TGF-beta system might constitute an effective therapeutic strategy.