Gregory Downey, MD, FRCPC, National Jewish Health and University of Colorado School of Medicine, Denver, CO, USA

Idiopathic Pulmonary Fibrosis (IPF) is a chronic, progressive and frequently fatal disorder for which nintedanib and pirfenidone have been shown to slow the rate of decline in lung function. However, responses are variable and side effects are common, and neither drug is curative. We used an in-silico data-driven approach, and identified a strong connection between the transcriptomic perturbations in IPF disease and those induced by saracatinib, a selective Src kinase inhibitor, originally developed for oncological indications. We investigated the anti-fibrotic efficacy of saracatinib in three preclinical models: (i) in vitro in normal human lung fibroblasts (NHLFs); (ii) in vivo in bleomycin and recombinant adenovirus transforming growth factor-beta (Ad-TGF-β) murine models of pulmonary fibrosis; and (iii) ex vivo in precision cut lung slices from these mouse models. In each model, saracatinib was equal to or superior than nintedanib or pirfenidone in blocking fibrogenic responses. These results led to an FDA-approved phase 1B/2A human clinical trial in the use of saracatinib in the treatment of IPF (STOP-IPF) that is currently ongoing.

Learning Objectives
At the end of this presentation, attendees will be able to:

  • Identify recent advances in the epidemiology and molecular basis of fibrosing interstitial lung diseases;
  • Describe the use of genomic and transcriptomic data to identify potential therapeutic targets for pulmonary fibrosis; and
  • Appraise results of preclinical studies in tissue culture and animal models and assess how these are applicable to human clinical trials in pulmonary fibrosis.

CanMEDS Roles Addressed: Collaborator, Communicator, Health Advocate, Leader, Medical Expert, Professional, Scholar

Chris Ryerson, MD, FRCPC
University of British Columbia, Vancouver, BC

This presentation will review recent data informing the pharmacological management of fibrotic interstitial lung disease and new approaches to management that are currently being studied.

Learning Objectives
At the end of this presentation, attendees will be able to:

  • Describe approaches to identifying progressive pulmonary fibrosis;
  • Identify features that impact the timing and choice of pharmacotherapy for progressive pulmonary fibrosis; and
  • Describe the outcomes of progressive pulmonary fibrosis.

CanMEDS Roles Addressed: Collaborator, Medical Expert, Professional, Scholar