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ID 62314
フルテキストURL
著者
Nishii, Kazuya Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Ohashi, Kadoaki Department of Respiratory Medicine, Okayama University Hospital ORCID Kaken ID researchmap
Watanabe, Hiromi Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Makimoto, Go Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Nakasuka, Takamasa Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Higo, Hisao Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Ninomiya, Kiichiro Department of Respiratory Medicine, Okayama University Hospital Kaken ID
Kato, Yuka Center for Innovative Clinical Medicine, Okayama University Hospital Kaken ID
Kubo, Toshio Center for Clinical Oncology, Okayama University Hospital Kaken ID researchmap
Rai, Kammei Department of Respiratory Medicine, Okayama University Hospital
Ichihara, Eiki Department of Respiratory Medicine, Okayama University Hospital Kaken ID publons
Hotta, Katsuyuki Center for Innovative Clinical Medicine, Okayama University Hospital Kaken ID publons researchmap
Tabata, Masahiro Center for Clinical Oncology, Okayama University Hospital Kaken ID researchmap
Maeda, Yoshinobu Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kaken ID researchmap
Kiura, Katsuyuki Department of Respiratory Medicine, Okayama University Hospital ORCID Kaken ID publons researchmap
抄録
Osimertinib, a third generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, is the standard treatment for patients with lung cancer harboring EGFR T790M; however, acquired resistance is inevitable due to genetic and epigenetic changes in cancer cells. In addition, a recent randomized clinical trial revealed that the combination of osimertinib and bevacizumab failed to exhibit superior progression‑free survival compared with osimertinib alone. The present study aimed to investigate the effect of triple therapy with osimertinib, bevacizumab and cetuximab in xenograft tumors with different initial tumor volumes (conventional model, 200 mm3 and large model, 500 mm3). The results demonstrated that osimertinib significantly inhibited tumor growth in both the conventional and large models; however, maximum tumor regression was attenuated in the large model in which hypoxia‑inducible factor‑1α (HIF‑1α) and transforming growth factor‑α (TGF‑α) expression levels increased. Although the combination of osimertinib and bevacizumab exerted a greater inhibitory effect on tumor growth compared with osimertinib in the conventional model, the effect of this combination therapy was attenuated in the large model. TGF‑α attenuated sensitivity to osimertinib in vitro; however, this negative effect was counteracted by the combination of osimertinib and cetuximab, but not osimertinib and bevacizumab. In the large xenograft tumor model, the triple therapy induced the greatest inhibitory effect on tumor growth compared with osimertinib alone and its combination with bevacizumab. Clinical trials of the triple therapy are required for patients with lung cancer with EGFR mutations and HIF‑1α/TGF‑α.
キーワード
epidermal growth factor receptor
osimertinib
bevacizumab
cetuximab
hypoxia‑inducible factor‑1α
transforming growth factor‑α
発行日
2021-7-7
出版物タイトル
Oncology Letters
22巻
3号
出版者
Spandidos Publications
開始ページ
639
ISSN
1792-1074
資料タイプ
学術雑誌論文
言語
English
OAI-PMH Set
岡山大学
著作権者
© Nishii et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
論文のバージョン
publisher
DOI
Web of Science KeyUT
関連URL
isVersionOf https://doi.org/10.3892/ol.2021.12900
ライセンス
https://creativecommons.org/licenses/by-nc-nd/4.0/
Citation
Nishii K, Ohashi K, Watanabe H, Makimoto G, Nakasuka T, Higo H, Ninomiya K, Kato Y, Kubo T, Rai K, Rai K, et al: Triple therapy with osimertinib, bevacizumab and cetuximab in EGFR‑mutant lung cancer with HIF‑1α/TGF‑α expression. Oncol Lett 22: 639, 2021
助成機関名
Japan Society for the Promotion of Science
助成番号
15H04830
オープンアクセス(出版社)
OA