WCLC 2025 - Posters & ePosters-P3.03.22 Tumor Treating Fields (TTFields) Downregulate DNA Repair and Show Efficacy in Small Cell Lung Carcinoma Preclinical Models

P3.03.22 Tumor Treating Fields (TTFields) Downregulate DNA Repair and Show Efficacy in Small Cell Lung Carcinoma Preclinical Models

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This preclinical study investigates the efficacy of Tumor Treating Fields (TTFields) combined with standard chemotherapy and immunotherapy in treating small cell lung cancer (SCLC), an aggressive lung cancer subtype with poor prognosis. TTFields are electric fields that disrupt cancer cell processes and are FDA-approved for glioblastoma, mesothelioma, and non-small cell lung cancer.<br /><br />In vitro experiments on human SCLC cell lines (DMS-53, H196) demonstrated that TTFields applied with cisplatin and etoposide chemotherapy significantly reduced cell count and colony formation more than either treatment alone. TTFields treatment downregulated proteins in the FA-BRCA DNA repair pathway (including BRCA2, FANCD2, FANCA), leading to increased DNA damage as evidenced by elevated γH2AX foci. This combination also induced immunogenic cell death, shown by calreticulin exposure, ATP release, and HMGB1 secretion, which may enhance antitumor immune responses.<br /><br />In vivo, TTFields treatment reduced tumor growth in a murine orthotopic SCLC model. When combined with cisplatin, etoposide, and anti-PD-L1 immunotherapy, tumor volume and weight were significantly decreased compared to controls or individual treatments. These results suggest synergistic effects of TTFields with chemotherapy and immune checkpoint blockade.<br /><br />The study concludes that TTFields have promising potential to improve SCLC treatment outcomes by inducing DNA damage, inhibiting DNA repair pathways, and promoting immunogenic cell death. The findings support further investigation into TTFields as an adjunct to current standard regimens combining chemotherapy and immunotherapy for SCLC patients.<br /><br />Presented at the World Conference on Lung Cancer 2025, the research highlights TTFields as a novel physical cancer therapy capable of enhancing chemotherapy efficacy and immune activation in this challenging malignancy.

Asset Subtitle

Tisdrey Torres

Meta Tag

Speaker Tisdrey Torres

Topic Tumor Biology – Translational Biology

Keywords

Tumor Treating Fields

TTFields

small cell lung cancer

SCLC

chemotherapy

immunotherapy

DNA damage

FA-BRCA pathway

immunogenic cell death

immune checkpoint blockade