Highlights on Future Treatments of IPF: Clues and Pitfalls

Abstract

Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease characterized by irreversible scarring of lung tissue, leading to death. Despite recent advancements in understanding its pathophysiology, IPF remains elusive, and therapeutic options are limited and non-curative. This review aims to synthesize the latest research developments, focusing on the molecular mechanisms driving the disease and on the related emerging treatments. Unfortunately, several phase 2 studies showing promising preliminary results did not meet the primary endpoints in the subsequent phase 3, underlying the complexity of the disease and the need for new integrated endpoints. IPF remains a challenging condition with a complex interplay of genetic, epigenetic, and pathophysiological factors. Ongoing research into the molecular keystones of IPF is critical for the development of targeted therapies that could potentially stop the progression of the disease. Future directions include personalized medicine approaches, artificial intelligence integration, growth in genetic insights, and novel drug targets.

Keywords: IPF; clinical trials; future perspective; idiopathic pulmonary fibrosis; molecular mechanism; pathogenesis; target therapies; therapy.

Figure 1

Overview of the most significant pathogenic pathways involved in the pathogenesis of idiopathic pulmonary fibrosis (IPF) and molecules currently under clinical investigation and their mechanisms of action within the pathways implicated in IPF pathogenesis. Legend: AEC: alveolar epithelial cells; EMT: epithelial-mesenchymal transition; PDE-4B: phosphodiesterase-4B; ECM: extracellular matrix; MAPK/ERK: mitogen-activated protein kinase/extracellular signal-regulated kinase; LPA1: lysophosphatidic acid receptor 1; C/EBPβ: CCAAT/enhancer binding protein beta; mAb: monoclonal antibody; Bcl-2: B-cell lymphoma 2; TGF-β: transforming growth factor beta; GF: growth factor; TNF-α: tumor necrosis factor alpha; IL: interleukin; OSMR: oncostatin M receptor; CSF-1R: colony stimulating factor 1 receptor; PD-L1: programmed death—ligand 1; Smad3: SMAD family member 3; MSCs: mesenchymal stem cells; STAT3: signal transducer and activator of transcription 3; JAK1/2: Janus kinase 1/2.