5yr
Exosome-derived miR-210 involved in resistance to osimertinib and epithelial-mesenchymal transition in EGFR mutant non-small cell lung cancer cells - PubMed
Source : https://pubmed.ncbi.nlm.nih.gov/33939301/
Background: Osimertinib is a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) approved for the treatment of patients with EGFR-mutant non-small cell lung cancer (NSCLC). However, the mechanisms of acquired drug resistance to osimertinib have not as yet been clarified. Exosomes and microRNAs (miRNAs) are involved in carcinogenesis and drug resistance in human cancers.
Key Points
• In the current preclinical study, researchers employed established osimertinib‐resistant HCC827 (HCC827‐OR) and PC‐9 (PC‐9‐OR) cells to assess the profiles of exosomal miRNA linked to resistance to osimertinib in EGFR‐mutant NSCLC cells.
• The authors concluded that “exosomes derived from osimertinib‐resistant, EGFR‐mutant NSCLC cells induced EMT and drug resistance in osimertinib‐sensitive cells via delivery of miR‐210. Exosomal miR‐210 may play an important role in the development of resistance to osimertinib in the tumor microenvironment and serve as a therapeutic target to conquer this resistance in EGFR‐mutant NSCLC.”
• The authors hypothesized that exosomes may be shed from drug‐resistant cells, in this way transferring mediators of drug resistance to drug‐sensitive cells and causing them to require the cancer drug‐resistant phenotype. Such mediators could include miRNAs and long non‐coding RNAs (lncRNAs), as well as proteins such as drug‐efflux pumps. Of note, MiR‐210 plays a role in various biological processes, including the DNA damage response, cell proliferation, angiogenesis, mitochondrial metabolism, and apoptosis.