Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5843959 | Pharmacology & Therapeutics | 2015 | 46 Pages |
Abstract
The TGFβ signaling pathway has pleiotropic functions regulating cell growth, differentiation, apoptosis, motility and invasion, extracellular matrix production, angiogenesis, and immune response. TGFβ signaling deregulation is frequent in tumors and has crucial roles in tumor initiation, development and metastasis. TGFβ signaling inhibition is an emerging strategy for cancer therapy. The role of the TGFβ pathway as a tumor-promoter or suppressor at the cancer cell level is still a matter of debate, due to its differential effects at the early and late stages of carcinogenesis. In contrast, at the microenvironment level, the TGFβ pathway contributes to generate a favorable microenvironment for tumor growth and metastasis throughout all the steps of carcinogenesis. Then, targeting the TGFβ pathway in cancer may be considered primarily as a microenvironment-targeted strategy. In this review, we focus on the TGFβ pathway as a target for cancer therapy. In the first part, we provide a comprehensive overview of the roles played by this pathway and its deregulation in cancer, at the cancer cell and microenvironment levels. We go on to describe the preclinical and clinical results of pharmacological strategies to target the TGFβ pathway, with a highlight on the effects on tumor microenvironment. We then explore the perspectives to optimize TGFβ inhibition therapy in different tumor settings.
Keywords
ECMMCP-1PSCCTGFTGFβPDGFMSIT-helperbFGFPBMCTNFαHGFT-regMMPT-regulatory cellHSCI-SmadCAFnatural killerHCCNOxROSPancreatic ductal adenocarcinomaPDAC یا pancreatic ductal adenocarcinomaAngiogenesisloss of heterozygosityNADPH oxidaseReactive oxygen specieinterferonIFNinterleukinoverall survivalMicrosatellite instabilitystable diseasetransforming growth factor-βtumor necrosis factor-αEMTNSCLCNon-small cell lung cancerPeripheral blood mononuclear cellHepatic stellate cellpancreatic stellate cellHepatocyte growth factorVascular endothelial growth factorVascular Endothelial Growth Factor (VEGF)Connective tissue growth factorplatelet-derived growth factorbasic fibroblast growth factorCancer-associated fibroblastsFibrosisLOHExtracellular matrixmatrix metalloproteinaseMetastasisMicroenvironmentPartial responsecomplete responseHepatocellular carcinomaepithelial-to-mesenchymal transition
Related Topics
Health Sciences
Pharmacology, Toxicology and Pharmaceutical Science
Pharmacology
Authors
Cindy Neuzillet, Annemilaï Tijeras-Raballand, Romain Cohen, Jérôme Cros, Sandrine Faivre, Eric Raymond, Armand de Gramont,