Targeting TGF beta signaling for cancer therapy

Abstract

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