Combination of carbon-ion beam and dual tyrosine kinase inhibitor, lapatinib, effectively destroys HER2 positive breast cancer stem-like cells.

To investigate whether carbon-ion beam alone, or in combination with lapatinib, has a beneficial effect in targeting HER2-positive breast cancer stem-like cells (CSCs) compared to that of X-rays, human breast CSCs derived from BT474 and SKBR3 cell lines were treated with a carbon-ion beam or X-rays irradiation alone or in combination with lapatinib, and then cell viability, spheroid formation assays, apoptotic analyses, gene expression analysis of related genes, and -H2AX foci were performed. Spheroid formation assays confirmed that ESA+/CD24- cells have CSC properties compared to ESA-/CD24+ cells. CSCs were more highly enriched after X-ray irradiation combined with lapatinib, whereas carbon-ion beam combined with lapatinib significantly decreased the proportion of CSCs.