Canertinib induces ototoxicity in three preclinical models

Jian Tang, Yi Qian, Hui Li, Benjamin J. Kopecky, Dalian Ding, Henry C. Ou, Rhonda DeCook, Xiaojie Chen, Zhenyu Sun, Megan Kobel, Jianxin Bao

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Neuregulin-1 (NRG1) ligand and its epidermal growth factor receptor (EGFR)/ERBB family regulate normal cellular proliferation and differentiation in many tissues including the cochlea. Aberrant NRG1 and ERBB signaling cause significant hearing impairment in mice. Dysregulation of the same signaling pathway in humans is involved in certain types of cancers such as breast cancer or non-small cell lung cancer (NSCLC). A new irreversible pan-ERBB inhibitor, canertinib, has been tested in clinical trials for the treatment of refractory NSCLC. Its possible ototoxicity was unknown. In this study, a significant dose-dependent canertinib ototoxicity was observed in a zebrafish model. Canertinib ototoxicity was further confirmed in two mouse models with different genetic backgrounds. The data strongly suggested an evolutionally preserved ERBB molecular mechanism underlying canertinib ototoxicity. Thus, these results imply that clinical monitoring of hearing loss should be considered for clinical testing of canertinib or other pan-ERBB inhibitors.

Original languageEnglish (US)
Pages (from-to)59-66
Number of pages8
JournalHearing Research
Volume328
DOIs
StatePublished - Oct 1 2015

Keywords

  • Canertinib
  • ERBB
  • NRG1
  • Non-small cell lung cancer
  • Ototoxicity
  • Outer hair cell

ASJC Scopus subject areas

  • Sensory Systems

Fingerprint Dive into the research topics of 'Canertinib induces ototoxicity in three preclinical models'. Together they form a unique fingerprint.

  • Cite this

    Tang, J., Qian, Y., Li, H., Kopecky, B. J., Ding, D., Ou, H. C., DeCook, R., Chen, X., Sun, Z., Kobel, M., & Bao, J. (2015). Canertinib induces ototoxicity in three preclinical models. Hearing Research, 328, 59-66. https://doi.org/10.1016/j.heares.2015.07.002