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Targeting the transforming growth factor-beta signaling pathway in human cancer Nagaraj NS; Datta PKExpert Opin Investig Drugs 2010[Jan]; 19 (1): 77-91The transforming growth factor-ss (TGF-beta) signaling pathway plays a pivotal role in diverse cellular processes. TGF-beta switches its role from a tumor suppressor in normal or dysplastic cells to a tumor promoter in advanced cancers. It is widely believed that the Smad-dependent pathway is involved in TGF-beta tumor-suppressive functions, whereas activation of Smad-independent pathways, coupled with the loss of tumor-suppressor functions of TGF-beta, is important for its pro-oncogenic functions. TGF-beta signaling has been considered a useful therapeutic target. The discovery of oncogenic actions of TGF-beta has generated a great deal of enthusiasm for developing TGF-beta signaling inhibitors for the treatment of cancer. The challenge is to identify the group of patients where targeted tumors are not only refractory to TGF-beta-induced tumor suppressor functions but also responsive to the tumor-promoting effects of TGF-beta. TGF-beta pathway inhibitors, including small and large molecules, have now entered clinical trials. Preclinical studies with these inhibitors have shown promise in a variety of different tumor models. Here, we focus on the mechanisms of signaling and specific targets of the TGF-beta pathway that are critical effectors of tumor progression and invasion. This report also examines the therapeutic intervention of TGF-ss signaling in human cancers.|Antineoplastic Agents/administration & dosage/adverse effects/pharmacology/*therapeutic use[MESH]|Clinical Trials as Topic[MESH]|Drug Discovery[MESH]|Humans[MESH]|Neoplasms/*drug therapy/metabolism[MESH]|Oligonucleotides, Antisense/administration & dosage/adverse effects/pharmacology/therapeutic use[MESH]|Signal Transduction/*drug effects[MESH]|Small Molecule Libraries/administration & dosage/pharmacology/therapeutic use[MESH]|Transforming Growth Factor beta/*antagonists & inhibitors[MESH] |
