Targeting TGFβ Signaling for Cancer Therapy

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