Radioresistance of the breast tumor is highly correlated to its level of cancer stem cell and its clinical implication for breast irradiation

Radiother Oncol. 2017 Sep;124(3):455-461. doi: 10.1016/j.radonc.2017.08.019. Epub 2017 Sep 17.

Abstract

Background and purpose: Growing evidence suggested the coexistence of cancer stem cells (CSCs) within solid tumors. We aimed to study radiosensitivity parameters for the CSCs and differentiated tumor cells (TCs) and the correlation of the fractions of CSCs to the overall tumor radioresistance.

Material and methods: Surviving fractions of breast cancer cell lines were analyzed using a dual-compartment Linear-quadratic model with independent fitting parameters: radiosensitive αTC, βTC, αCSC, βCSC, and fraction of CSCs f. The overall tumor radio-resistance, the biological effective doses and tumor control probability were estimated as a function of CSC fraction for different fractionation regimens. The pooled clinical outcome data were fitted to the single- and dual-compartment linear-quadric models.

Results: CSCs were more radioresistant characterized by smaller α compared to TCs: αTC=0.1±0.2, αCSC=0.04±0.07 for MCF-7 (f=0.1%), αTC=0.08±0.25, αCSC=0.04±0.18 for SUM159PT (f=2.46%). Higher f values were correlated with increasing radioresistance in cell lines. Analysis of clinical outcome data is in accordance of a dual-compartment CSC model prediction. Higher percentage of BCSCs resulted in more overall tumor radioresistance and less biological effectiveness.

Conclusions: Percentage of CSCs strongly correlated to overall tumor radioresistance. This observation suggested potential individualized radiotherapy to account for heterogeneous population of CSCs and their distinct radiosensitivity for breast cancer.

Keywords: Cancer stem cell; Dual-compartment model; Linear-quadratic model; Radioresistance; Tumor cell.

MeSH terms

  • Breast / radiation effects*
  • Breast Neoplasms / pathology
  • Breast Neoplasms / radiotherapy*
  • Cell Line, Tumor
  • Cell Survival / radiation effects
  • Dose Fractionation, Radiation
  • Female
  • Humans
  • Neoplastic Stem Cells / pathology*
  • Radiation Tolerance*