Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0034069 (pulmonary fibrosis)
 7,050 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Imatinib mesylate is a potent and specific tyrosine kinase inhibitor against c-ABL, BCR-ABL, and c-KIT, and has been demonstrated to be highly active in chronic myeloid leukemia and gastrointestinal stromal tumors. We examined the antifibrotic effects of imatinib using a bleomycin-induced lung fibrosis model in mice because imatinib also inhibits tyrosine kinase of platelet-derived growth factor receptors (PDGFRs). Imatinib inhibited the growth of primary murine lung fibroblasts and the autophosphorylation of PDGFR-beta induced by PDGF. Administration of imatinib significantly prevented bleomycin-induced pulmonary fibrosis in mice, partly by reducing the number of mesenchymal cells incorporating bromodeoxyuridine. Analysis of bronchoalveolar lavage cells demonstrated that imatinib did not suppress early inflammation on Days 7 and 14 caused by bleomycin. These results suggest that imatinib has the potential to prevent pulmonary fibrosis by inhibiting the proliferation of mesenchymal cells, and that imatinib might be useful for the treatment of pulmonary fibrosis in humans.
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PMID:Imatinib as a novel antifibrotic agent in bleomycin-induced pulmonary fibrosis in mice. 1573 62

Pulmonary toxicity is rarely seen with most commonly used targeted therapies. The endothelial growth factor receptor (EGFR) small-molecule tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib can cause interstitial lung disease (ILD). BCR-ABL tyrosine kinase inhibitors imatinib and dasatinib can cause pleural effusions. Infusion-related bronchospasm is common with the monoclonal antibodies to EGFR cetuximab and panitumumab, and case reports of bronchiolitis and pulmonary fibrosis have been described. Up to one-sixth of patients taking mammalian target of rapamycin (mTOR) inhibitors get a reversible interstitial pneumonitis. Bevacizumab, the monoclonal antibody to vascular endothelial growth factor (VEGF), has been associated with hemoptysis and pulmonary embolism particularly in patients with squamous cell lung cancer. Infusion-related bronchospasms, acute respiratory distress syndrome (ARDS), and interstitial pneumonitis can be seen with the anti-lymphocyte monoclonal antibodies rituximab, ofatumumab, and alemtuzumab. While most pulmonary toxicities from these therapies are mild and resolve promptly with dose reduction or discontinuation, it is important for the clinician to recognize these potential toxicities when faced with treatment-related complications. Discerning these pulmonary adverse effects may help in making decisions on diagnostic testing and therapy, particularly for those with pulmonary and cardiovascular co-morbidities.
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PMID:Pulmonary toxicities from targeted therapies: a review. 2207 88