The Influence of EGFR Inactivation on the Radiation Response in High Grade Glioma.

Anica Dricu,Stefan-Alexandru Artene,Ligia Tataranu,Oana Alexandru,Stefana Purcaru,Cristian Tuţă,Catalin Folcuţi,Juan Castro,Laura Lucan

doi:10.3390/ijms19010229

Abstract

Lack of effectiveness of radiation therapy may arise from different factors such as radiation induced receptor tyrosine kinase activation and cell repopulation; cell capability to repair radiation induced DNA damage; high grade glioma (HGG) tumous heterogeneity, etc. In this study, we analyzed the potential of targeting epidermal growth factor receptor (EGFR) in inducing radiosensitivity in two human HGG cell lines (11 and 15) that displayed similar growth patterns and expressed the receptor protein at the cell surface. We found that 15 HGG cells that express more EGFR at the cell surface were more sensitive to AG556 (an EGFR inhibitor), compared to 11 HGG cells. Although in line 15 the effect of the inhibitor was greater than in line 11, it should be noted that the efficacy of this small-molecule EGFR inhibitor as monotherapy in both cell lines has been modest, at best. Our data showed a slight difference in the response to radiation of the HGG cell lines, three days after the treatment, with line 15 responding better than line 11. However, both cell lines responded to ionizing radiation in the same way, seven days after irradiation. EGFR inhibition induced radiosensitivity in 11 HGG cells, while, in 15 HGG cells, the effect of AG556 treatment on radiation response was almost nonexistent.

Highlights

The clinical oncology landscape has changed dramatically in the last decades with the introduction of targeted therapy and, more recently, to the addition of immunotherapy
We found that high grade glioma (HGG) cells respond differentially to ionizing radiation, two of three HGG cell lines studied being resistant, while one HGG cell line was sensitive to ionizing radiation [35,36]
Our data showed a slight difference in the response to radiation of the HGG cell lines, with HGG line 15 presenting a slightly improved response when compared to HGG cell line 11 after three days, while seven days after the treatment the response presented by both cell lines was similar, with the exception of the Gy radiation dose, which produced a stronger cytotoxic effect in the HGG cell line

Summary

Introduction

The clinical oncology landscape has changed dramatically in the last decades with the introduction of targeted therapy and, more recently, to the addition of immunotherapy. A distinct group of malignant gliomas, called astrocytomas are derived from astrocytes and are the most numerous and the most aggressive malignancies of the Central Nervous System (CNS). Astrocytomas have been classified by the World Health Organization (WHO) on the basis of hystology and prognosis into two categories: low grade gliomas (LGG) and high grade gliomas (HGG). LGG are comprised of grade I (pylocitic astrocytomas) and grade II (diffuse astrocytomas) and generally slow-progressing tumors with an overall good prognosis. HGG are comprised of grade III (anaplastic astrocytomas) and grade IV (glioblastomas) (GBMs), which are both the most numerous and the most aggressive tumors of the CNS, being considered incurable in 99% of the cases. Despite the groundbreaking progress made, treatment for some malignancies, such as GBMs, has remained almost completely unchanged for the better part of the last 10 years

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