Emerging therapeutic targets for idiopathic pulmonary fibrosis: preclinical progress and therapeutic implications

2021 ◽  
Author(s):  
Toyoshi Yanagihara ◽  
Ciaran Scallan ◽  
Kjetil Ask ◽  
Martin RJ Kolb
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Therapeutic Targets ◽  
Therapeutic Implications

scholarly journals Idiopathic pulmonary fibrosis: Epithelial-mesenchymal interactions and emerging therapeutic targets

2018 ◽  
Vol 71-72 ◽  
pp. 112-127 ◽  
Author(s):  
Justin C. Hewlett ◽  
Jonathan A. Kropski ◽  
Timothy S. Blackwell
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Therapeutic Targets

Oxidative/nitrosative stress, autophagy and apoptosis as therapeutic targets of melatonin in idiopathic pulmonary fibrosis

2018 ◽  
Vol 22 (12) ◽  
pp. 1049-1061 ◽  
Author(s):  
Azam Hosseinzadeh ◽  
Seyed Ali Javad-Moosavi ◽  
Russel J. Reiter ◽  
Rasoul Yarahmadi ◽  
Habib Ghaznavi ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Nitrosative Stress ◽  
Therapeutic Targets

scholarly journals Therapeutic targets in idiopathic pulmonary fibrosis

2017 ◽  
Vol 131 ◽  
pp. 49-57 ◽  
Author(s):  
Martin Kolb ◽  
Francesco Bonella ◽  
Lutz Wollin
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Therapeutic Targets

scholarly journals Immune Stroma in Lung Cancer and Idiopathic Pulmonary Fibrosis: A Common Biologic Landscape?

2021 ◽  
Vol 22 (6) ◽  
pp. 2882
Author(s):  
Sara Lettieri ◽  
Tiberio Oggionni ◽  
Andrea Lancia ◽  
Chandra Bortolotto ◽  
Giulia Maria Stella
Keyword(s):  
Lung Cancer ◽  
Cancer Therapy ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Immune Checkpoint ◽  
Paradigm Shift ◽  
Checkpoint Inhibition ◽  
Immune Checkpoint Inhibition ◽  
Immune Microenvironment ◽  
Therapeutic Implications

Idiopathic pulmonary fibrosis (IPF) identifies a specific entity characterized by chronic, progressive fibrosing interstitial pneumonia of unknown cause, still lacking effective therapies. Growing evidence suggests that the biologic processes occurring in IPF recall those which orchestrate cancer onset and progression and these findings have already been exploited for therapeutic purposes. Notably, the incidence of lung cancer in patients already affected by IPF is significantly higher than expected. Recent advances in the knowledge of the cancer immune microenvironment have allowed a paradigm shift in cancer therapy. From this perspective, recent experimental reports suggest a rationale for immune checkpoint inhibition in IPF. Here, we recapitulate the most recent knowledge on lung cancer immune stroma and how it can be translated into the IPF context, with both diagnostic and therapeutic implications.

scholarly journals What role for asbestos in idiopathic pulmonary fibrosis? Findings from the IPF job exposures study

2021 ◽  
Author(s):  
Carl J Reynolds ◽  
Rupa Sisodia ◽  
Chris Barber ◽  
Cosetta Minelli ◽  
Sara De Matteis ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Asbestos Exposure ◽  
Minor Allele ◽  
Cumulative Exposure ◽  
Environment Interaction ◽  
Therapeutic Implications ◽  
Gene Environment Interaction ◽  
Link Type ◽  
Gene Environment

AbstractRationaleAsbestos is posited to cause otherwise ‘idiopathic’ pulmonary fibrosis (IPF); establishing this has important diagnostic and therapeutic implications.ObjectivesTo determine the association between occupational asbestos exposure and IPF; to investigate interaction with MUC5B rs35705950 genotype.MethodsMulti-centre, incident case-control study. Cases (n=494) were men diagnosed with IPF at 21 United Kingdom hospitals. Controls (n=466) were age-matched men who attended a hospital clinic in the same period. Asbestos exposure was measured using a validated job exposure matrix and a source-receptor model. The primary outcome was the association between asbestos exposure and IPF, estimated using logistic regression adjusted for age, smoking and centre. Interaction with MUC5B rs3570950 was investigated using a genetic dominant model.Measurements and Main Results327 (66%) cases and 293 (63%) controls ever had a high or medium asbestos exposure risk job; 8% of both cases and controls, had cumulative exposure estimates ≥ 25 fibre.ml−1.years. Occupational asbestos exposure was not associated with IPF, adjusted OR 1.1(95%CI 0.8-1.4; p=0.6) and there was no gene-environment interaction (p=0.2). Ever smoking was associated with IPF, OR 1.4 (95%CI 1-1.9; p=0.04). When stratifying for genotype there was significant interaction between smoking and work in an exposed job (p<0.01) for carriers of the minor allele of MUC5B rs3570950.ConclusionsOccupational asbestos exposure alone, or through interaction with MUC5B rs35705950 genotype, was not associated with IPF. However, exposure to asbestos and smoking interact to increase IPF risk in carriers of the minor allele of MUC5B rs3570950.Clinical trial registered with www.clinicaltrials.gov (NCT03211507).

scholarly journals Identification of Targetable Kinases in Idiopathic Pulmonary Fibrosis

2021 ◽  
Author(s):  
Hisao Higo ◽  
Kadoaki Ohashi ◽  
Shuta Tomida ◽  
Sachi Okawa ◽  
Hiromasa Yamamoto ◽  
...  
Keyword(s):  
Gene Expression ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Expression Analysis ◽  
Gene Expression Analysis ◽  
Therapeutic Targets ◽  
Integrated Analysis ◽  
Potential Candidate ◽  
Tissue Samples ◽  
Kinase Expression

Abstract Background: Tyrosine kinase activation plays an important role in the progression of pulmonary fibrosis. In this study, we analyzed the expression of 612 kinase-coding and cancer-related genes using next-generation sequencing to identify potential therapeutic targets for idiopathic pulmonary fibrosis (IPF).Methods: Thirteen samples from five patients with IPF (Cases 1-5) and eight samples from four patients without IPF (control) were included in this study. Six of the thirteen samples were obtained from different lung segments of a single patient who underwent bilateral pneumonectomy. Gene expression analysis of IPF lung tissue samples (n=13) and control samples (n=8) was performed using SureSelect RNA Human Kinome Kit. The expression of the selected genes was further confirmed at the protein level by immunohistochemistry (IHC).Results: Gene expression analysis revealed a correlation between the gene expression signatures and the degree of fibrosis, as assessed by Ashcroft score. In addition, the expression analysis indicated a stronger heterogeneity among the IPF lung samples than among the control lung samples. In the integrated analysis of the 21 samples, DCLK1 and STK33 were found to be upregulated in IPF lung samples compared to control lung samples. However, the top most upregulated genes were distinct in individual cases. DCLK1, PDK4, and ERBB4 were upregulated in IPF case 1, whereas STK33, PIM2, and SYK were upregulated in IPF case 2. IHC revealed that these proteins were expressed in the epithelial layer of the fibrotic lesions.Conclusions: We performed a comprehensive kinase expression analysis to explore the potential therapeutic targets for IPF. DCLK1 and STK33 can serve as potential candidate targets for molecular targeted therapy of IPF. In addition, PDK4, ERBB4, PIM2, and SYK may serve as personalized therapeutic targets of IPF.

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