Transforming growth factor-? (TGF-?), an extensively investigated cytokine, plays a very important role in promoting the spread of cancers in the body, and can play a direct role in facilitating metastasis. Consequently, TGF-? is currently explored as a prognostic candidate biomarker of tumor invasiveness and metastasis. Therefore, in clinical scenarios involving increased TGF-? activity, attempts to decrease or abrogate TGF-? signaling could be used as a therapy for advanced or metastatic disease. It follows that TGF-? signaling offers an attractive target for cancer therapy. Several anti-TGF-? approaches, such as TGF-? antibodies, antisense oligonucleotides and small molecules inhibitors of TGF-? type 1 receptor kinase, have shown great promise in the preclinical studies. These studies, coupled with progressing clinical trials indicate that inhibition of TGF-? signaling may be indeed a viable option to cancer therapy. This review summarizes the TGF-? biology, screening cancer patients for anti-TGF-? therapy, and several strategies targeted against TGF-? signaling for cancer therapy. The next several years promise to improve our understanding of approaching cancer therapy by further evaluation of TGF-? signaling inhibitors for clinical efficacy. The complexity of TGF-? biology guarantees that many surprises lie ahead.
Epigenetic Targeting of Transforming Growth Factor β Receptor II and Implications for Cancer Therapy
