title: Halofuginone for fibrosis, regeneration and cancer in the gastrointestinal tract.
abstract: Organ fibrosis and architectural remodeling can severely disrupt tissue function, often with fatal consequences. Fibrosis is the end result of chronic inflammatory reactions induced by a variety of stimuli, and the key cellular mediator of fibrosis comprises the myofibroblasts which, when activated, serve as the primary collagen-producing cells. Complex links exist between fibrosis, regeneration and carcinogenesis, and the concept that all organs contain common tissue fibrosis pathways that could be potential therapeutic targets is an attractive one. Because of the major impact of fibrosis on human health there is an unmet need for safe and effective therapies that directly target fibrosis. Halofuginone inhibits tissue fibrosis and regeneration, and thereby affects the development of tumors in various tissues along the gastrointestinal tract. The high efficacy of halofuginone in reducing the fibrosis that affects tumor growth and tissue regeneration is probably due to its dual role in inhibiting the signaling pathway of transforming growth factor β, on the one hand, and inhibiting the development of Th17 cells, on the other hand. At present halofuginone is being evaluated in a clinical trial for other fibrotic indication, and any clinical success in that trial would allow the use of halofuginone, also for all other fibrotic indications, including those of the gastrointestinal tract.
authors.affiliation: Mark Pines, Institute of Animal Sciences, the Volcani Center, Bet Dagan 50250, Israel.
authors.forename: Mark
authors.initials: M
authors.lastname: Pines
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D004066:Digestive System Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D004067:Digestive System Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D005355:Fibrosis; D005765:Gastrointestinal Agents / Q000627:therapeutic use*; D041981:Gastrointestinal Tract / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D010880:Piperidines / Q000627:therapeutic use*; D052999:Quinazolinones / Q000627:therapeutic use*; D012038:Regeneration / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D005765:Gastrointestinal Agents; D010880:Piperidines; D052999:Quinazolinones; C010176:halofuginone
keywords: Cancer; Extracellular matrix; Myofibroblast; Stellate cell; Transforming growth factor β