Potential of combination therapy with lenvatinib and radiation for thyroid cancer

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  • Suzuki Kensuke
    Department of Otolaryngology, Head and Neck Surgery, Kansai Medical University
  • Iwai Hiroshi
    Department of Otolaryngology, Head and Neck Surgery, Kansai Medical University
  • Utsunomiya Keita
    Department of Radiology, Kansai Medical University
  • Kono Yumiko
    Department of Radiology, Kansai Medical University
  • Kobayashi Yoshiki
    Department of Otolaryngology, Head and Neck Surgery, Kansai Medical University
  • Yun Yasutaka
    Department of Otolaryngology, Head and Neck Surgery, Kansai Medical University
  • Mitani Akitoshi
    Department of Otolaryngology, Head and Neck Surgery, Kansai Medical University
  • Fukui Kenta
    Department of Otolaryngology, Head and Neck Surgery, Kansai Medical University
  • Sakai Haruka
    Department of Otolaryngology, Head and Neck Surgery, Kansai Medical University
  • Tanigawa Noboru
    Department of Radiology, Kansai Medical University
  • Kanda Akira
    Department of Otolaryngology, Head and Neck Surgery, Kansai Medical University Department of Laboratory Medicine, Laboratory Medicine Center, Kansai Medical University Hospital

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Other Title
  • レンバチニブ併用放射線療法による新たな甲状腺癌治療の可能性
  • レンバチニブ ヘイヨウ ホウシャセン リョウホウ ニ ヨル アラタ ナ コウジョウセン ガン チリョウ ノ カノウセイ

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Abstract

<p>Patients with differentiated thyroid cancer usually have good prognosis, while those with advanced disease often develop local recurrences or distant metastases, resulting in poor clinical outcomes. The main treatment options for unresectable differentiated thyroid cancer are radioactive iodine (131I) therapy and tyrosine kinase inhibitors. However, many advanced patients become refractory to radioactive iodine and tyrosine kinase inhibitors have a high incidence of treatment-related adverse events. We investigated the synergistic effects of the combination with the molecular targeted agent lenvatinib and external beam radiation using differentiated thyroid cancer cells and its xenograft mouse model. The combination with lenvatinib and external beam radiation markedly inhibited cell proliferation in vitro and tumor growth in nude mice, suggesting a synergistic treatment effect. Immunofluorescence analysis and immunohistochemistry with a cell proliferation marker Ki-67 showed that the expressions of Ki-67 were decreased in the combination therapy group. The combination therapy also induced apoptosis, G2/M phase cell cycle arrest and increased intracellular uptake of lenvatinib, which may contribute to the synergistic antitumor effect. Combination therapy with lenvatinib and radiation including external beam radiation and 131I, suggests a powerful and tolerable new therapeutic strategy for advanced thyroid cancer.</p>

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