Transforming growth factor-β: Biology and application to cancer therapy

Abstract

Transforming growth factor-β (TGF-β), 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-β is currently explored as a prognostic candidate biomarker of tumor invasiveness and metastasis. Therefore, in clinical scenarios involving increased TGF-β activity, attempts to decrease or abrogate TGF-β signaling could be used as a therapy for advanced or metastatic disease. It follows that TGF-β signaling offers an attractive target for cancer therapy. Several anti-TGF-β approaches, such as TGF-β antibodies, antisense oligonucleotides and small molecules inhibitors of TGF-β type 1 receptor kinase, have shown great promise in the preclinical studies. These studies, coupled with progressing clinical trials indicate that inhibition of TGF-β signaling may be indeed a viable option to cancer therapy. This review summarizes the TGF-β biology, screening cancer patients for anti-TGF-β therapy, and several strategies targeted against TGF-β signaling for cancer therapy. The next several years promise to improve our understanding of approaching cancer therapy by further evaluation of TGF-β signaling inhibitors for clinical efficacy. The complexity of TGF-β biology guarantees that many surprises lie ahead. © 2009, Oncology Institute of Vojvodina.