論文

国際誌
2021年9月

Triple therapy with osimertinib, bevacizumab and cetuximab in EGFR-mutant lung cancer with HIF-1α/TGF-α expression.

Oncology letters
  • Kazuya Nishii
  • Kadoaki Ohashi
  • Hiromi Watanabe
  • Go Makimoto
  • Takamasa Nakasuka
  • Hisao Higo
  • Kiichiro Ninomiya
  • Yuka Kato
  • Toshio Kubo
  • Kammei Rai
  • Eiki Ichihara
  • Katsuyuki Hotta
  • Masahiro Tabata
  • Yoshinobu Maeda
  • Katsuyuki Kiura
  • 全て表示

22
3
開始ページ
639
終了ページ
639
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.3892/ol.2021.12900

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.

リンク情報
DOI
https://doi.org/10.3892/ol.2021.12900
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/34386061
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8299008
ID情報
  • DOI : 10.3892/ol.2021.12900
  • PubMed ID : 34386061
  • PubMed Central 記事ID : PMC8299008

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