The interplay of reactive oxygen species and the epidermal growth factor receptor in tumor progression and drug resistance

Meng Shih Weng, Jer Hwa Chang, Wen Yueh Hung, Yi Chieh Yang, Ming Hsien Chien

Research output: Contribution to journalReview articlepeer-review

80 Citations (Scopus)


Background: The epidermal growth factor receptor (EGFR) plays important roles in cell survival, growth, differentiation, and tumorigenesis. Dysregulation of the EGFR is a common mechanism in cancer progression especially in non-small cell lung cancer (NSCLC). Main body: Suppression of the EGFR-mediated signaling pathway is used in cancer treatment. Furthermore, reactive oxygen species (ROS)-induced oxidative stress from mitochondrial dysfunction or NADPH oxidase (NOX) overactivation and ectopic expression of antioxidative enzymes were also indicated to be involved in EGFR-mediated tumor progression (proliferation, differentiation, migration, and invasion) and drug resistance (EGFR tyrosine kinase inhibitor (TKI)). The products of NOX, superoxide and hydrogen peroxide, are considered to be major types of ROS. ROS are not only toxic materials to cells but also signaling regulators of tumor progression. Oxidation of both the EGFR and downstream phosphatases by ROS enhances EGFR-mediated signaling and promotes tumor progression. This review primarily focuses on the recent literature with respect to the roles of the EGFR and ROS and correlations between ROS and the EGFR in tumor progression and EGFR TKI resistance. Short conclusion: The evidence discussed in this article can serve as a basis for basic and clinical research to understand how to modulate ROS levels to control the development and drug resistance of cancers.

Original languageEnglish
Article number61
JournalJournal of Experimental and Clinical Cancer Research
Issue number1
Publication statusPublished - Mar 16 2018


  • Drug resistance
  • Epidermal growth factor receptor
  • NADPH oxidase
  • Oxidation
  • Reactive oxygen species
  • Tumor progression

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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