Open Access

Osimertinib (AZD9291) increases radio‑sensitivity in EGFR T790M non‑small cell lung cancer

  • Authors:
    • Nannan Wang
    • Linlin Wang
    • Xiangjiao Meng
    • Jia Wang
    • Lifang Zhu
    • Changting Liu
    • Shaorong Li
    • Li Zheng
    • Zhenfan Yang
    • Ligang Xing
    • Jinming Yu
  • View Affiliations

  • Published online on: October 17, 2018     https://doi.org/10.3892/or.2018.6803
  • Pages: 77-86
  • Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Osimertinib (AZD9291) is a third generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that has demonstrated significant clinical benefits in patients with EGFR‑sensitizing mutations or the T790M mutation. However, the potential therapeutic effect of osimertinib combined with ionizing irradiation (IR) is not well understood. The present study investigated treatment with osimertinib combined with IR in EGFR T790M non‑small cell lung cancer (NCI‑H1975) in vitro and in vivo. The results revealed that osimertinib inhibited proliferation and clonogenic survival following irradiation, decreased G2/M phase arrest in irradiated cells, and delayed DNA damage repair in a concentration‑ and time‑dependent manner. Furthermore, osimertinib alone or in combination with IR, blocked the phosphorylation of EGFR (Tyr1068/Tyr1173), protein kinase B and extracellular signal‑regulated kinase. Osimertinib also enhanced the antitumor activity of IR in tumor‑bearing nude mice. The results of the present study indicated that osimertinib has therapeutic potential as a radiation‑sensitizer in lung cancer cells harboring the EGFR T790M mutation, providing a rationale for clinically combining osimertinib with irradiation in EGFR T790M non‑small cell lung cancer.
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January-2019
Volume 41 Issue 1

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Copy and paste a formatted citation
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Spandidos Publications style
Wang N, Wang L, Meng X, Wang J, Zhu L, Liu C, Li S, Zheng L, Yang Z, Xing L, Xing L, et al: Osimertinib (AZD9291) increases radio‑sensitivity in EGFR T790M non‑small cell lung cancer. Oncol Rep 41: 77-86, 2019.
APA
Wang, N., Wang, L., Meng, X., Wang, J., Zhu, L., Liu, C. ... Yu, J. (2019). Osimertinib (AZD9291) increases radio‑sensitivity in EGFR T790M non‑small cell lung cancer. Oncology Reports, 41, 77-86. https://doi.org/10.3892/or.2018.6803
MLA
Wang, N., Wang, L., Meng, X., Wang, J., Zhu, L., Liu, C., Li, S., Zheng, L., Yang, Z., Xing, L., Yu, J."Osimertinib (AZD9291) increases radio‑sensitivity in EGFR T790M non‑small cell lung cancer". Oncology Reports 41.1 (2019): 77-86.
Chicago
Wang, N., Wang, L., Meng, X., Wang, J., Zhu, L., Liu, C., Li, S., Zheng, L., Yang, Z., Xing, L., Yu, J."Osimertinib (AZD9291) increases radio‑sensitivity in EGFR T790M non‑small cell lung cancer". Oncology Reports 41, no. 1 (2019): 77-86. https://doi.org/10.3892/or.2018.6803