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

Area of Science:

• Oncology
• Pulmonology
• Pharmacology

Background:

• Idiopathic pulmonary fibrosis (IPF) and lung cancer (LC) share molecular and cellular processes.
• Nintedanib, a tyrosine-kinase inhibitor, is approved for IPF treatment and was initially developed for cancer due to its anti-angiogenic properties.

Purpose of the Study:

• To perform a bioinformatic analysis of tyrosine kinases targeted by nintedanib.
• To identify common molecular pathways modulated by nintedanib in both LC and IPF.
• To highlight microRNAs influencing key signaling pathways and disease mechanisms.

Main Methods:

• Bioinformatic analysis of targeted tyrosine kinases.
• In vitro studies of nintedanib.
• Comparison with previous studies on microRNAs in LC and IPF.

Main Results:

• Nintedanib modulates key signaling pathways including MAPK, PI3K/AKT, JAK/STAT, TGF-β, VEGF, and WNT/β-catenin.
• These pathways involve intercellular adherence junctions and central carbon metabolism.
• Five microRNAs were identified influencing VEGF-A signaling and epithelial-to-mesenchymal transition.

Conclusions:

• Nintedanib targets shared molecular pathways relevant to both IPF and LC.
• The identified microRNAs correlate with the development of both diseases.
• This study provides insights into the molecular links between IPF and LC modulated by nintedanib.