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

TL;DR

This study demonstrates that inhibiting ERK and p38 MAPK pathways can decrease the radio-resistance of breast cancer stem cells to pulsed proton beam therapy, suggesting a potential combined treatment strategy.

Contribution

The paper reveals that ERK and p38 MAPK inhibitors can sensitize breast cancer stem cells to pulsed proton beam radiation, a novel approach to overcoming radio-resistance.

Findings

CSC resistance to pulsed proton beams confirmed

ERK and p38 inhibitors reduce CSC radio-resistance

Potential for combined therapy in breast cancer treatment

Abstract

Recent studies have identified highly tumorigenic cells with stem cell-like characteristics in human cancers, termed cancer stem cells (CSCs). CSCs are resistant to conventional radiotherapy and chemotherapy owing to their high DNA repair ability and oncogene overexpression. However, the mechanisms regulating CSC radio-resistance, particularly proton beam resistance, remain unclear. We isolated CSCs from the breast cancer cell lines MCF-7 and MDA-MB-231, which expressed the characteristic breast CSC membrane protein markers CD44+/CD24-/low, and irradiated the CSCs with pulsed proton beams. We confirmed that CSCs are resistant to pulsed proton beams and showed that treatment with p38 and ERK inhibitors reduced CSC radioresistance. Based on these results, BCSC radio-resistance can be reduced during proton beam therapy by co-treatment with ERK1/2 or p38 inhibitors, representing a novel approach for breast cancer therapy.