Common molecular pathways targeted by nintedanib in cancer and IPF: A bioinformatic study

Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease (ILD) sharing various genetic, molecular and cell processes with lung cancer (LC). Nintedanib, a tyrosine-kinase inhibitor, was first developed as an anticancer drug because it suppresses angiogenesis. It was then recognized as an anti-fibrotic agent and approved for the treatment of IPF. On the basis of in vitro studies of the drug, we performed a bioinformatic analysis of all targeted tyrosine kinases with the aim of highlighting common molecular pathways modulated by the drug in LC and IPF. The results show that MAPK, PI3K/AKT, JAK/STAT, TGF-beta, VEGF and WNT/beta-catenin signalling are the main molecular pathways modulated by the drug. Interestingly, these pathways include that controlled by intercellular adherence junctions (compromised in LC and IPF), and by central carbon metabolism (usually studied more in relation to the pathogenesis of cancer than IPF). On the basis of the tyrosine kinases considered, our bioinformatic analysis highlighted five microRNAs influencing VEGF-A signalling and epithelial to mesenchymal transition mechanisms. Comparison of our results with those of previous studies highlighted correlations between microRNAs and the development of LC and IPF.