Targeting TGFbeta signaling for cancer therapy.

Transforming growth factor (TGF) betas are multifunctional polypeptides that regulate several cellular functions, including cell growth and differentiation, extra cellular matrix production, motility and immunosuppression. The growth-inhibiting properties of TGFbeta have gained much attention into its role as a tumor suppressor. There is, however, now increasing evidence that TGFbeta switches roles, from tumor suppressor to tumor promoter, as the tumor progresses. Given the integral role of TGFbeta in the tumor progression, it follows that TGFbeta signaling offers an attractive target for cancer therapy. Several strategies including the use of antisense oligonucleotides for TGFbeta, TGFbeta antibodies, dominant negative TGFbeta receptor II, and small drug-molecules to inhibit TGFbeta receptor I kinase have shown great promise in the preclinical studies. These new findings, coupled with progressing clinical trials indicate that inhibition of TGFbeta signaling may, indeed, be a viable option to cancer therapy. This review summarizes the TGFbeta signaling, the dual role of TGFbeta--as a tumor suppressor and tumor promoter, and various strategies targeted against TGFbeta signaling for cancer therapy. The next few years promise to better our understanding of approaching cancer therapy with an eye to the inhibition of TGFbeta signaling.