Rbio-08. Investigating the Efficacy and Mechanisms of Tumor Treating Fields in Radiation-resistant Glioblastoma Models
Year: 2024
Type: conference-abstract
Abstract: Glioblastoma (GBM) is an aggressive malignant brain tumor with poor prognosis despite current treatment regimens involving surgical resection, radiation, temozolomide, and the newly approved use of Tumor Treating Fields (TTFields; a noninvasive, transdermal, administration of alternating low-intensity, intermediate-frequency electrical fields). Acquired radiation resistance, thought to be partially driven by brain tumor-initiating cells (BTICs), underscores therapeutic challenges in GBM. While clinical evidence supports the therapeutic benefit of TTFields, its precise mechanisms of action are poorly understood, and TTFields impact on radiation-resistant GBM is unknown. To better understand the effect and mechanism of TTFields in radiation-resistant GBM, we utilized patient-derived xenolines (PDX) and their acquired radio-resistant pairs to assess changes in viability and molecular signaling. PDX were previously developed by subcutaneous implantation of patient GBM cells into immunodeficient (nu/nu) mice. Acquired radiation-resistant PDX were generated through serial in vivo radiation. TTFields were administered with the Novocure inovitroTM device in a cooling incubator to maintain 37oC sample temperature in the ceramic well plates of the device. PDX were cultured on geltrex-coated coverslips under serum-free conditions. Cytotoxicity was quantified 72h post TTFields with crystal violet. Molecular signaling was captured with PamChip peptide-based kinase activity arrays and RayBiotech proteomic arrays. We found that TTFields inhibit cell growth in both parental and acquired radiation-resistant PDX. Differences in molecular signatures between the PDX lines suggest molecular mechanisms of TTFields sensitivity signatures and interactions with acquired radio-resistant PDX. We are currently trying to generate TTFields-resistant PDX lines through serial treatment with plans to examine BTIC populations relative to TTFields efficacy. We also plan to explore targetable TTFields-induced alterations in the future.
Source: Neuro-Oncology
Authors: Taylor Schanel, Rhea Pandit, Joshua Anderson, Hasan Alrefai, Amber Jones, Patricia Hicks, Anita Hjelmeland, Christopher Willey
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W4404237483