Clarity and Challenges in Tissue Fibrosis

Excerpt

The tremendous progress in understanding the mechanisms of tissue fibrosis has led to realistic hopes for effective antifibrotic therapies in a range of diseases, including hepatic fibrosis, idiopathic pulmonary fibrosis, and renal fibrosis, as well as fibrotic disorders of muscle, heart, skin and bone marrow. Common mechanisms across these different tissues have unearthed targets that may be relevant to many organs. Best understood are pathways leading to hepatic fibrosis, which also predispose to hepatocellular carcinoma. Hepatic stellate cells are the principal fibrogenic cells in the liver following their activation into myofibroblasts, and their detailed characterization has unearthed many targets for therapy. Increasingly, investigators now rely on genetic mouse models to define contributions of specific molecules, in hopes of antagonizing these molecules as therapeutic targets. Both genomic and molecular approaches are unveiling new patterns of gene expression and molecules. A robust framework for antifibrotic drug discovery has been developed, and many agents are in clinical trials. With iterative evaluation of drug candidates in both animal models and humans, accelerated progress in bringing these drugs to patients is anticipated.