CSIG-41. SENSITIZING CANCER CELLS TO TUMOR TREATING FIELDS (TTFIELDS) BY INHIBITION OF PI3K

Abstract Tumor Treating Fields (TTFields) are alternating electric fields, which disrupt cellular process critical for cancer cell survival and tumor progression. TTFields therapy is approved the treatment of glioblastoma (GBM) unresectable malignant pleural mesothelioma, being tested in clinical studies other solid tumors, including ovarian cancer, non-small lung carcinoma (NSCLC), hepatocellular (HCC). The current study aimed to detect potential mechanisms that may reduce sensitivity TTFields, target these pathways order re-sensitize cells TTFields. Cancer (Ovarian A2780, GBM U-87 MG, NSCLC H1299) display reduced were generated by continuous long-term application (7 or 13 days, depending on line). A Luminex multiplex assay revealed activation PI3K/AKT/mTOR signaling pathway cells, with significant increases phosphorylation levels AKT RPS6. This elevation was also observed immunohistochemistry sections from N1S1 HCC tumor-bearing rats treated relative sham. Treatment PI3K inhibitors re-sensitized them downregulated AKT. Concomitant inhibitor alpelisib mice orthotopically implanted MOSE-L firefly luciferase (FFL) resulted enhanced efficacy, as determined In Vivo Imaging System (IVIS) measurements volume. Overall, this demonstrated involved re-sensitization be achieved relevant inhibitors. results provide a rationale further examining benefit concomitant