Current models of pulmonary fibrosis for future drug discovery efforts

Expert Opin Drug Discov. 2020 Aug;15(8):931-941. doi: 10.1080/17460441.2020.1755252. Epub 2020 May 12.

Abstract

Introduction: Pulmonary fibrosis includes several lung disorders characterized by progressive fibrosis, of which idiopathic pulmonary fibrosis (IPF) is a particularly severe form with a median survival time of 3-5 years after diagnosis. Although numerous compounds have shown efficacy in attenuating pulmonary fibrosis using animal models, only a few compounds have shown their beneficial effects for IPF in clinical trials. Thus, there is an emergent need to improve the preclinical development process to better identify, characterize and select clinically useful targets.

Areas covered: In this review, the authors extensively describe current models of pulmonary fibrosis, including rodent models, ex vivo models, and in vitro models.

Expert opinion: Based upon our current understanding, improving the identification and characterization of clinically relevant molecules or pathways responsible for progressive fibrotic diseases and use of the appropriate preclinical model system to test these will likely be required to improve the drug development pipeline for pulmonary fibrosis. Combination with appropriate preclinical models with ex vivo (precision-cut lung slices) or in vitro models would be beneficial for high-throughput drug discovery or validation of drug effects.

Keywords: Fibrosis; cell culture; experimental models; tissue.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Disease Models, Animal
  • Drug Development*
  • Drug Discovery*
  • Drug Evaluation, Preclinical / methods
  • High-Throughput Screening Assays
  • Humans
  • Idiopathic Pulmonary Fibrosis / drug therapy
  • Idiopathic Pulmonary Fibrosis / physiopathology
  • Pulmonary Fibrosis / drug therapy*
  • Pulmonary Fibrosis / physiopathology
  • Severity of Illness Index
  • Survival Rate