CCRG-04. TARGETING THE CELL-CYCLE EFFECTS OF TUMOR TREATING FIELDS (TTFIELDS) TO INCREASE ITS EFFICACY

Abstract Tumor Treating Fields (TTFields) are a novel, non-invasive FDA-approved treatment modality for glioblastoma (GBM) that utilises alternating electric fields. Our research aims to elucidate the effect of TTFields on cell cycle advance understanding and find novel targets increasing its efficacy. We studied progression using live-cell imaging (inovitro Live™) PIP-FUCCI-transduced GBM cells, EdU incorporation, RPA foci fiber assay (in U251-MG, SNB-19, A172). These tools allow us track individual cells evaluate time spent in each phase, study ultimate fate control conditions concerning replication fork dynamics. Statistical testing was performed by 2-way ANOVA, Tukey-corrected multiple comparisons, Kruskal-Wallis test. causes an immediate delay S G2 with subsequent G1 arrest. Wee1 inhibition AZD1775 forces through S-phase abrogates TTFields-induced G2-checkpoint, preventing DNA repair. Combined led decreased incorporation increase S-phase-specific phospho-RPA foci. reduced significantly length after 12, 24, 48 72 hrs exposure (10.2, 8.3, 7.1 5.6 vs 13 um), also asymmetry at these points (0.56, 0.45, 0.49, 0.47 0.9 ratio) respectively. CombiningTTFields either Wee1, ATR, or Chk1 synergistically clonogenic survival. induced effects induction stress, which is aggravated Wee1. Additionally, dramatically boost efficacy vitro. This combination strategy has promising clinical potential will be tested vivo different xenografts. Cell signaling pathways