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.

Keywords: Stellate cell, Myofibroblast, Transforming growth factor β, Extracellular matrix, Cancer

Core tip: Fibrosis is a pathological process associated with excessive deposition of extracellular matrix that leads to destruction of organ architecture and function. Fibrosis contributes enormously to deaths worldwide, thus therapies are of a great need. The concept of common fibrosis pathways that could be therapeutic targets in all organs is an attractive one. Halofuginone is a novel anti-fibrotic therapy that inhibits tissue fibrosis, regeneration, and development of tumors in tissues along the gastrointestinal tract. At present halofuginone is being evaluated in a clinical trial for another fibrotic indication, and any clinical success there would allow its use for all other fibrotic indications.