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Enhanced anti-tumor effects of combined electric fields, cabozantinib, and radiation therapy in metastatic renal cell carcinoma

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Abstract

Purpose

This study aimed to evaluate the therapeutic potential of combining cabozantinib, electric fields (EFs; also called Tumor Treating Fields [TTFields]), and radiation in the treatment of metastatic renal cell carcinoma (RCC), focusing on overcoming resistance to conventional monotherapeutic regimens.

Methods

Human renal cancer cell lines (A498, Caki-1) were treated with cabozantinib (10 µM) for at least 6 h, TTFields (200 kHz, 0.8 V/cm) for 24 h, and radiation (3 Gy), both individually and in combination. Cellular responses, including proliferation, apoptosis, and metastatic potential, were analyzed by flow cytometry and Transwell assays.

Results

The combination of cabozantinib, TTFields, and radiation exhibited synergistic effects, significantly reducing cell proliferation, enhancing apoptosis, and suppressing metastatic capacity compared with individual treatments. Triple therapy resulted in marked inhibition of metastasis-related markers and changes in apoptotic profiles compared with the control group.

Conclusion

This multimodal therapy demonstrated superior efficacy in reducing the metastatic potential and prolonging the survival of RCC cells, offering a promising approach to overcoming treatment resistance in patients with metastatic RCC.

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Data availability

No datasets were generated or analyzed during the current study.

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Acknowledgements

This work was supported by National Research Foundation of Korea (NRF) grants funded by the Korean government (MSIT) (Grant Nos. NRF-2021R1A2C2008695 and NRF-2022R1A2C1010337). This work was also supported by a Korea Medical Device Development Fund grant funded by the Korean Government (the Ministry of Science and ICT, the Ministry of Trade, Industry and Energy, the Ministry of Health & Welfare, and the Ministry of Food and Drug Safety) (Project No.1711196423, RS-2023-00254868).

Funding

The authors declare that no funds, grants, or other support was received during the preparation of this manuscript.

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Authors and Affiliations

  1. Department of Bio-Medical Engineering, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul, 02841, Korea

    Jinju Heo & Myonggeun Yoon

  2. Institute of Global Health Technology (IGHT), Korea University, Seoul, Republic of Korea

    Yunhui Jo

  3. FieldCure Ltd, Seoul, 02852, Republic of Korea

    Myonggeun Yoon

Authors
  1. Jinju Heo
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  2. Yunhui Jo
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Jin-ju Heo. The first draft of the manuscript was written by Jin-ju Heo and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Myonggeun Yoon.

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Heo, J., Jo, Y. & Yoon, M. Enhanced anti-tumor effects of combined electric fields, cabozantinib, and radiation therapy in metastatic renal cell carcinoma. Clin Transl Oncol (2025). https://doi.org/10.1007/s12094-025-03898-x

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