Targeting TGFβ signaling for cancer therapy

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