The standard of care for advanced
non-small cell lung cancer (NSCLC) consists in
cisplatin-
combination chemotherapy. In patients bearing
tumors with activating mutations of the
epidermal growth factor receptor (EGFR), the inhibition of the EGFR intracellular
tyrosine kinase can induce up to 80 % response rates. However, both therapeutic strategies will eventually lead to recurrent disease due to the development of drug resistance. The identification of rare
cancer stem-like cells able to repopulate the
tumor, after failure to standard treatment modalities, has led to characterize these cells as potential therapeutic targets. This article will address the role of the CD133/
EpCAM stem cell-related markers and explore cell sensitivity to
cisplatin and to the EGFR-
tyrosine kinase inhibitor,
afatinib. Three human NSCLC cell lines, one wild-type (A549) and two harboring EGFR mutations (H1650 and H1975), as well as 20 NSCLC primary cultures, were grown in non-differentiating culture conditions for stem cell enrichment. Flow-cytometry analyses of CD133 and
EpCAM and cell sensitivity to
cisplatin and
afatinib were performed. Moreover, the expression of activated EGFR was assessed by Western blot. The cell lines and primary cultures grown in non-differentiating culture conditions were enriched with CD133/
EpCAM-positive cells and were significantly more resistant to
cisplatin and more sensitive to
afatinib as compared to the differentiated counterpart. In addition, increased EGFR-phosphorylation in non-differentiated cultures was observed. The present findings suggest that
afatinib might be beneficial for patients bearing
tumors with constitutively activated EGFR, to target chemo-resistant CD133/
EpCAM-positive cancer stem cells.