Novel drug targets in idiopathic pulmonary fibrosis

Introduction: Idiopathic pulmonary fibrosis (IPF) is a fatal, fibrosing interstitial pneumonia of unknown cause, that arises with progressive worsening in lung function. Several pathways were assumed to be involved in its pathogenesis and various molecules, targeting the differing mechanisms, have been investigated. To date, the most likely scenario is that the driving process is an aberrant wound healing response as a result of repeated alveolar epithelial cell (AEC) micro-injuries, that lead to lung remodeling. Thus, the only drugs approved for the treatment of IPF are two disease-modifying, anti-fibrotic molecules.Areas covered: This review provides a comprehensive summary of the current investigational drugs targeting pro-fibrotic and immune pathways, and cell-based therapy. Ongoing and completed trials are purposed through updated data.Expert opinion: Novel phase I and II trial results promote the paradigm of fibrosis-driven process against the inflammatory-based model previously proposed. The anti-fibrotic approved drugs, nintedanib and pirfenidone, are still an intriguing research topic. Meanwhile, multiple novel therapies, with more precise anti-fibrotic mechanisms than in the past, are under evaluation. Given the heterogeneity of IPF, multi-target therapies are likely to be most effective and validation of biomarkers of treatment is needed. At the moment, enrolment in a clinical trial may be the best chance for IPF patients to cure the disease.