title: Targeting aberrant TGF-beta signaling in pre-clinical models of cancer.
abstract: The TGF-beta signaling pathway is central to the control of diverse biological processes including cellular proliferation, cell survival, apoptosis, extracellular matrix deposition/remodeling, migration, invasion and immune regulation/inflammation. Given the pleiotropic effects of this cytokine, it comes as no surprise that numerous pathological conditions are associated with alterations in the TGF-beta pathway, including chronic fibrosis, airway remodeling (asthma), cardiovascular disease and cancer. Thus, there are increasing efforts to develop reagents and therapeutic strategies to impair TGF-beta signaling. Here we review several classes of inhibitors, including knock-down strategies aimed at signaling components of the TGF-beta pathway, TGF-beta neutralizing antibodies, TGF-beta receptor extracellular domains that function as ligand traps and small molecule kinase inhibitors. Strategies with potential for application as anti-cancer therapeutics that have been evaluated in pre-clinical animal models will be discussed. TGF-beta action is complex, shifting from a tumor suppressor to a promoter of tumor cell invasion and metastasis in several types of cancer. This raises important issues regarding not only the status of the TGF-beta pathway in the individual patient but also the precise stage during disease progression that such inhibitors should be employed. Potential consequences of targeting the TGF-beta pathway will also be considered.
authors: Department of Medicine, McGill University, Montréal, Québec, Canada.
authors: Anna Alexeyevna
authors: AA
authors: Mourskaia
authors: Jason Jonathan
authors: JJ
authors: Northey
authors: Peter Michael
authors: PM
authors: Siegel
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D004353:Drug Evaluation, Preclinical; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors*
chemical_list: D000970:Antineoplastic Agents; D016212:Transforming Growth Factor beta