Rdna-02. Tumor Treating Fields Differentially Alter Homologous Recombination in Patient Derived Glioma Cells Versus Established Lines
Year: 2018
Type: conference-abstract
Abstract: Within the heterogeneous tumor cell population there exists a subpopulation exhibiting stem-like properties known as glioma stem cells(GSCs) which are thought to be prime contributors in tumor resilience. Low-frequency alternating electric fields, tumor treating fields(TTFs), have recently emerged as a novel form of radiotherapy with FDA approval for the treatment of glioblastoma. We sought to determine the anti-proliferative effects of TTFs using a panel of 4 patient-derived GSCs and established lines, U87 and U373. Using the Novocure Inovitro system, cells were treated with 200kHz TTFs for 72hr and the cell number was determined using a Vi-Cell Cell Viability Analyzer. We found a statistically significant reduction in cell growth following TTF exposure for 4 of the 6 cell lines tested. The size of the anti-proliferative effect was cell line dependent and varied between 15 and 30%. We examined the effect of TTFs on the DNA damage response following irradiation utilizing immunofluorescent foci staining kinetics coupled with high-throughput automated imaging and analysis. Our initial results demonstrated a varied response among the tested cell lines. A 48hr TTF application increased the number of 53bp1 foci above background in U87 and two of the tested GSCs. TTF application for 24hr prior to irradiation was found to systematically reduce the number of induced Rad51 repair foci. However, an increased number of persistent Rad51 foci in the established lines was measured, indicative of reduced repair. In contrast, within the GSCs, the initial reduction in Rad51 foci was maintained throughout the 24hr repair time course. Our preliminary results have demonstrated the efficacy of TTFs to reduce cancerous cell proliferation in vitro while uncovering a differential DNA damage modulation response between established lines and GSCs. Future studies will focus on elucidating the mechanism of GSC TTF resistance with the goal of increasing treatment efficacy via multi-modal combination therapy.
Source: Neuro-Oncology
Institution: The University of Texas MD Anderson Cancer Center
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2900280640