重粒子治療適応拡大に向けた薬物併用療法の基礎的研究 (J103)

Tumors that overexpress the receptor tyrosine kinase HER2 (HER2-positive tumors) tend to be higher grade tumors that are more likely to spread and thus are more aggressive than other types of breast cancers (BCs). In this study we investigated 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. Spheroid formation assays confirmed that ESA+/CD24- cells have CSC properties compared to ESA-/CD24+ cells. We found that 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. Carbon-ion beam combined with lapatinib significantly enhanced apoptosis-related expression of caspase-3 compared to carbon-ion beam alone, X-rays alone, or X-rays combined with lapatinib. In conclusion, carbon ion beam combined with lapatinib has high potential to eliminate breast CSCs with enhanced apoptosis.