Radiosensitivity Differences between EGFR Mutant and Wild-Type Lung Cancer Cells are Larger at Lower Doses

Int J Mol Sci. 2019 Jul 25;20(15):3635. doi: 10.3390/ijms20153635.

Abstract

In the era of precision medicine, radiotherapy strategies should be determined based on genetic profiles that predict tumor radiosensitivity. Accordingly, pre-clinical research aimed at discovering clinically applicable genetic profiles is needed. However, how a given genetic profile affects cancer cell radiosensitivity is unclear. To address this issue, we performed a pilot in vitro study by utilizing EGFR mutational status as a model for genetic profile. Clonogenic assays of EGFR mutant (n = 6) and wild-type (n = 9) non-small cell lung carcinoma (NSCLC) cell lines were performed independently by two oncologists. Clonogenic survival parameters SF2, SF4, SF6, SF8, mean inactivation dose (MID), D10, D50, α, and β were obtained using the linear quadratic model. The differences in the clonogenic survival parameters between the EGFR mutant and wild-type cell lines were assessed using the Mann-Whitney U test. As a result, for both datasets, the p values for SF2, SF4, D50, α, and α/β were below 0.05, and those for SF2 were lowest. These data indicate that a genetic profile of NSCLC cell lines might be predictive for their radiation response; i.e., EGFR mutant cell lines might be more sensitive to low dose- and low fraction sized-irradiation.

Keywords: clonogenic assays; gene mutations; precision medicine; radiation therapy; radiosensitivity.

MeSH terms

  • Cell Line, Tumor
  • Cell Survival / radiation effects
  • Dose-Response Relationship, Radiation
  • ErbB Receptors / genetics
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / radiotherapy
  • Mutation*
  • Radiation Dosage*
  • Radiation Tolerance / genetics*
  • Tumor Stem Cell Assay
  • X-Rays

Substances

  • EGFR protein, human
  • ErbB Receptors