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ID 62314
Author
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
Abstract
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.
Keywords
epidermal growth factor receptor
osimertinib
bevacizumab
cetuximab
hypoxia‑inducible factor‑1α
transforming growth factor‑α
Note
This is an open access article distributed under the terms of Creative Commons Attribution License.
Published Date
2021-7-7
Publication Title
Oncology Letters
Volume
volume22
Issue
issue3
Publisher
Spandidos Publications
Start Page
639
ISSN
1792-1074
Content Type
Journal Article
language
英語
OAI-PMH Set
岡山大学
Copyright Holders
© Nishii et al.
File Version
publisher
DOI
Web of Science KeyUT
Related Url
isVersionOf https://doi.org/10.3892/ol.2021.12900
License
https://creativecommons.org/licenses/by-nc-nd/4.0/
Funder Name
Japan Society for the Promotion of Science
助成番号
15H04830
Open Access (Publisher)
OA