このエントリーをはてなブックマークに追加
ID 61841
FullText URL
fulltext.pdf 1.31 MB
Author
Watanabe, Hiromi Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
Ichihara, Eiki Department of Allergy and Respiratory Medicine, Okayama University Hospital Kaken ID publons
Kayatani, Hiroe 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
Ninomiya, Kiichiro Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kaken ID
Nishii, Kazuya 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
Ando, Chihiro Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
Okawa, Sachi 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
Kano, Hirohisa Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences ORCID
Hara, Naofumi Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
Hirabae, Atsuko Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
Kato, Yuka Center for Innovative Clinical Medicine, Okayama University Hospital Kaken ID
Ninomiya, Takashi Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
Kubo, Toshio Center for Clinical Oncology, Okayama University Hospital Kaken ID researchmap
Rai, Kammei Department of Allergy and Respiratory Medicine, Okayama University Hospital
Ohashi, Kadoaki Department of Allergy and Respiratory Medicine, Okayama University Hospital ORCID Kaken ID researchmap
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 Allergy and Respiratory Medicine, Okayama University Hospital ORCID Kaken ID publons researchmap
Abstract
Molecular agents targeting the epidermal growth factor receptor (EGFR)-, anaplastic lymphoma kinase (ALK)- or c-ros oncogene 1 (ROS1) alterations have revolutionized the treatment of oncogene-driven non-small-cell lung cancer (NSCLC). However, the emergence of acquired resistance remains a significant challenge, limiting the wider clinical success of these molecular targeted therapies. In this study, we investigated the efficacy of various molecular targeted agents, including erlotinib, alectinib, and crizotinib, combined with anti-vascular endothelial growth factor receptor (VEGFR) 2 therapy. The combination of VEGFR2 blockade with molecular targeted agents enhanced the anti-tumor effects of these agents in xenograft mouse models of EGFR-, ALK-, or ROS1-altered NSCLC. The numbers of CD31-positive blood vessels were significantly lower in the tumors of mice treated with an anti-VEGFR2 antibody combined with molecular targeted agents compared with in those of mice treated with molecular targeted agents alone, implying the antiangiogenic effects of VEGFR2 blockade. Additionally, the combination therapies exerted more potent antiproliferative effects in vitro in EGFR-, ALK-, or ROS1-altered NSCLC cells, implying that VEGFR2 inhibition also has direct anti-tumor effects on cancer cells. Furthermore, VEGFR2 expression was induced following exposure to molecular targeted agents, implying the importance of VEGFR2 signaling in NSCLC patients undergoing molecular targeted therapy. In conclusion, VEGFR2 inhibition enhanced the anti-tumor effects of molecular targeted agents in various oncogene-driven NSCLC models, not only by inhibiting tumor angiogenesis but also by exerting direct antiproliferative effects on cancer cells. Hence, combination therapy with anti-VEGFR2 antibodies and molecular targeted agents could serve as a promising treatment strategy for oncogene-driven NSCLC.
Published Date
2021-01-07
Publication Title
Cancer science
Publisher
Wiley
ISSN
1347-9032
NCID
AA11808050
Content Type
Journal Article
language
英語
OAI-PMH Set
岡山大学
Copyright Holders
© 2021 The Authors.
File Version
publisher
PubMed ID
NAID
DOI
Web of Science KeyUT
Related Url
isVersionOf https://doi.org/10.1111/cas.14801
License
https://creativecommons.org/licenses/by-nc-nd/4.0/