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Purpose <p>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.</p> Methods <p>Human renal cancer cell lines (A498, Caki-1) were treated with cabozantinib (10&#xa0;µM) for at least 6&#xa0;h, TTFields (200&#xa0;kHz, 0.8&#xa0;V/cm) for 24&#xa0;h, and radiation (3&#xa0;Gy), both individually and in combination. Cellular responses, including proliferation, apoptosis, and metastatic potential, were analyzed by flow cytometry and Transwell assays.</p> Results <p>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.</p> Conclusion <p>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.</p>

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

  • 期刊论文

  • 发表日期：

    2025年3月24日

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  • Jinju Heo,
  • Yunhui Jo,
  • Myonggeun Yoon

摘要

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.