TUMOUR TREATING FIELDS WITH DDR INHIBITORS EFFECTIVELY LEADS TO CHEMO-/RADIO-SENSITISATION OF GLIOMAS

Abstract AIMS High grade gliomas are the most common CNS malignancies and cause ~200,000 deaths/year globally. Glioblastoma (WHO IV) confer worst prognoses with their treatment being hindered by glioma stem cell-like (GSC) tumour sub-regions high intratumoural spatio-heterogeneity. Tumour Treating Fields (TTFields) exert clinically approved alternating electric fields of intermediate frequency which induces anti-mitotic effects within concomitant deleterious on cellular responses to DNA damage (DDR). Therefore, resistance could be overcome TTFields developed DDR inhibitors (DDRi) chemo-/radio- sensitisation. METHOD Surgically resected samples derived from core invasive edge were processed create GSC cell lines, offering highly relevant models. These grown in either 2D or 3D-printed AlvetexTM scaffolds, treated DDRi, subjected chemo-/radio-therapy then placed under (200 kHz, 48- 72 hrs). Survival was measured clonogenic assays after 3 weeks. Immunofluorescence western blot analysis used analyse combination DDR. RESULTS DDRi led significant chemo/radio-sensitisation both 3D intratumoral core/edge Western immunofluorescence analyses revealed that heightened treatments lesion resolution impaired. CONCLUSIONS concurrent effectively leads chemo-/radio-sensitisation GSCs model spatio-heterogeneity is thought impede effcacy. Given all BBB penetrable clinical trials, additionally compliment these regimens boost