Cytotoxicity and inhibitory potential of CUDC-101 in non-small cell lung cancer cells with rare EGFR L861Q mutation

Abstract

The epidermal growth factor receptor (EGFR) represents an effective target for the treatment of non-small cell lung cancer. In the treatment of classical EGFR mutations, EGFR tyrosine kinase inhibitors have achieved desirable clinical efficacy. However, the effectiveness of tyrosine kinase inhibitors (TKIs) against the L861Q mutation has not been fully established. In this study, the four cell lines containing the L861Q mutation were constructed by CRISPR and the anti-tumour effects of CUDC-101 on them were investigated in vitro by various chemosensitivity methods, with afatinib serving as a positive control. The results demonstrated that CUDC-101 inhibited the proliferation and clonogenic capacity on the four cells through the ERK or AKT pathways, decreased the mitochondrial membrane potential of the cells, blocked the cell cycle and promoted apoptosis. Our findings suggest that CUDC-101 may be a promising treatment option for NSCLC patients with the EGFR exon 18 substitution mutation L861Q.

Keywords

• L861Q
• CUDC-101
• Mutation
• Proliferation
• Cytotoxicology