2022 World Conference on Lung Cancer (ePosters)-EP16.03-028. Cancer Cells May be Re-sensitized to Tumor Treating Fields (TTFields) Through Inhibition of the PI3K/AKT/mTOR Pathway

EP16.03-028. Cancer Cells May be Re-sensitized to Tumor Treating Fields (TTFields) Through Inhibition of the PI3K/AKT/mTOR Pathway

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This study examined the potential of combining Tumor Treating Fields (TTFields) therapy with inhibitors of the PI3K/AKT/mTOR pathway to enhance treatment efficacy in cancer cells. TTFields are alternating electric fields that have anti-mitotic effects on cancer cells. They are currently approved for the treatment of newly diagnosed glioblastoma, recurrent glioblastoma, and unresectable malignant pleural mesothelioma.<br /><br />The researchers found that long-term exposure to TTFields resulted in reduced sensitivity of cancer cells to the therapy. However, these desensitized cells were still significantly affected by the anti-proliferative effect of TTFields. The PI3K/AKT/mTOR signaling pathway was found to be activated in response to long-term TTFields application, leading to increased phosphorylation of key proteins in both in vitro and in vivo studies.<br /><br />To overcome this reduced sensitivity, the researchers explored the combination of TTFields with PI3K inhibitors. It was observed that co-application of TTFields with PI3K/mTOR dual or pan- and isoform-specific inhibitors of PI3K resulted in increased treatment efficacy compared to TTFields or inhibitor alone in all combination groups.<br /><br />The study provides evidence that the PI3K/AKT/mTOR signaling pathway reduces sensitivity to TTFields and suggests that targeting this pathway could enhance the effectiveness of TTFields therapy in patients. The researchers used various methods including cytotoxicity assays, LUMINEX technology, immunohistochemistry, western blotting, and in vivo imaging to investigate the effects of TTFields and PI3K inhibitors on cancer cells.<br /><br />In conclusion, this study highlights the potential of combining TTFields therapy with targeted inhibition of the PI3K/AKT/mTOR pathway to improve the treatment outcomes for cancer patients. Further research and clinical trials are needed to validate these findings and explore the efficacy of this combination therapy in different types of cancer.

Asset Subtitle

Moshe Giladi

Meta Tag

Speaker Moshe Giladi

Topic Tumour Biology and Biomarkers - Molecular Profiling and Targeted Therapies

Keywords

Tumor Treating Fields

TTFields therapy

PI3K/AKT/mTOR pathway

cancer cells

glioblastoma

malignant pleural mesothelioma

sensitivity

PI3K inhibitors

treatment efficacy

combination therapy