This review describes the challenges created by the existence of multiple molecular pathways leading to fibrosis and proposes that attention be focused on targeting the fibroblasts and myofibroblasts which themselves produce multiple cytokines and growth factors as well as the extracellular matrix, which is the hallmark of fibrotic lung disease.
The last 20 years have seen remarkable progress in our understanding of the molecular pathogenesis of pulmonary fibrosis leading to multiple programmes in drug discovery, and there are currently 15 actively recruiting trials registered on http://www.clinicaltrials.gov. Unfortunately, at this time only one new drug, pirfenidone, has progressed to approval for use in patients. Part of the frustration is that drugs that are effective in targeting inflammatory pathways have been ineffective in lung fibrosis. This may result from the inability to treat patients early in the disease process but it is also likely that pathways independent of inflammation can drive fibrosis.
We further propose that this approach should inhibit fibrosis independent of cell type or the signalling cascade that is activating these cells. We are hopeful that the next 20 years will see many more therapeutic options for patients suffering with fibrotic lung disease.
aImmunology Research, Janssen Research & Development, LLC, Pennsylvania, USA
bCentre for Respiratory Research, Division of Medicine, UCL, London
cClinical Sciences, Division of Medicine, University of Nottingham, Nottingham, UK
Correspondence to Paschalis Ntolios, MD, MSc, Centre for Respiratory Disease, 5 University Street, London WC1E 6JF, UK. Tel: +44 20 7679 6976, +44 74284 70755; e-mail: firstname.lastname@example.org