Tumor treating fields induced senescence on glioblastoma

Am J Cancer Res. 2023 Nov 15;13(11):5626-5640. eCollection 2023.

Abstract

Innovative approaches have given rise to a method for treating newly diagnosed GBM cancer patients within a span of 4.9 months, resulting in improved median overall survival (OS) and minimal side effects during the phase III clinical trial. This approach is referred to as Tumor Treating Fields (TTFields). The objective of this study is to ascertain the potential of TTFields treatment in sensitizing GBM cancer cells by enhancing TTFields-induced senescence. To achieve this, the research employed a multifaceted methodology that encompassed several elements, including the analysis of SA-β-gal staining, flow cytometry, Western blotting, morphology assessment, Positron Emission Tomography (PET)/Computed Tomography (CT), immunohistochemical staining, and microassay. Over a period of up to 5 days, the number of cells exhibiting senescence-specific morphology and positive SA-β-Gal activity progressively increased. These findings indicate that p16, p21, p27 and pRB are pivotal regulators of TTFields-induced senescence through NF-κB activation. The outcomes reveal that TTFields treatment effectively promotes TTFields-induced senescence in GBM cells through a mechanism independent of apoptosis. In conclusion, this research underscores the viability of this treatment approach as a reliable protocol to address the limitations associated with the conventional GBM treatment.

Keywords: Tumor-treating fields; glioblastoma; senescence.