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Recent studies have identified highly tumorigenic cells with stem cell-likecharacteristics in human cancers, termed cancer stem cells (CSCs). CSCs areresistant to conventional radiotherapy and chemotherapy owing to their high DNArepair ability and oncogene overexpression. However, the mechanisms regulatingCSC radio-resistance, particularly proton beam resistance, remain unclear. Weisolated CSCs from the breast cancer cell lines MCF-7 and MDA-MB-231, whichexpressed the characteristic breast CSC membrane protein markersCD44+/CD24-/low, and irradiated the CSCs with pulsed proton beams. We confirmedthat CSCs are resistant to pulsed proton beams and showed that treatment withp38 and ERK inhibitors reduced CSC radioresistance. Based on these results,BCSC radio-resistance can be reduced during proton beam therapy by co-treatmentwith ERK1/2 or p38 inhibitors, representing a novel approach for breast cancertherapy.

ERK/p38 MAPK inhibition reduces radio-resistance to pulsed proton beam in breast cancer stem cells cells