Targeting TGF-ß signaling in cancer.

ABSTRACT

INTRODUCTION: The transforming growth factor-ß (TGF-ß) signaling pathway has a pivotal role in tumor suppression and yet, paradoxically, in tumor promotion. Functional context dependent insights into the TGF-ß pathway are crucial in developing TGF-ß-based therapeutics for cancer. AREAS COVERED This review discusses the molecular mechanism of the TGF-ß pathway and describes the different ways of tumor suppression by TGF-ß. It is then explained how tumors can evade these effects and how TGF-ß contributes to further growing and spreading of some of the tumors. In the last part of the review, the data on targeting TGF-ß pathway for cancer treatment is assessed. This review focuses on anti-TGF-ß based treatment and other options targeting activated pathways in tumors where the TGF-ß tumor suppressor pathway is lost. Pre-clinical as well up to date results of the most recent clinical trials are given. EXPERT OPINION Targeting the TGF-ß pathway can be a promising direction in cancer treatment. However, several challenges still exist, the most important are differentiating between the carcinogenic effects of TGF-ß and its other physiological roles, and delineating the tumor suppressive versus the tumor promoting roles of TGF-ß in each specific tumor. Future studies are needed in order to find safer and more effective TGF-ß-based drugs.