Anti-tumor Effect of Neratinib Against Lung Cancer Cells Harboring Oncogene Alterations

Overview

Journal Oncol Lett

Specialty Oncology

Date 2019 Mar 12

PMID 30854046

Citations 13

Authors

Yusuke Ogoshi

Kazuhiko Shien

Takahiro Yoshioka

Hidejiro Torigoe

Hiroki Sato

Masakiyo Sakaguchi

Shuta Tomida

Kei Namba

Eisuke Kurihara

Yuta Takahashi

Ken Suzawa

Hiromasa Yamamoto

Junichi Soh

Shinichi Toyooka

Affiliations

Soon will be listed here.

Abstract

Human epidermal growth factor receptor 2 (HER2) is a member of the ErbB family of receptor tyrosine kinases. Numerous studies have reported the amplification and overexpression of HER2 in several types of cancer, including non-small cell lung cancer (NSCLC). However, the benefits of HER2-targeted therapy have not been fully established. In the present study, the anti-tumor effect of neratinib, an irreversible pan-HER tyrosine kinase inhibitor (TKI), against NSCLC cells harboring alterations was investigated. The sensitivity of normal bronchial epithelial cells (BEAS-2B) ectopically overexpressing wild-type or mutant to neratinib was assessed. Furthermore, the anti-tumor activity of neratinib in several NSCLC cell lines harboring alterations was determined and , and the association between their genetic alterations and sensitivity to neratinib treatment was investigated. BEAS-2B cells ectopically overexpressing wild-type or mutants (A775insYVMA, G776VC, G776LC, P780insGSP, V659E, G660D and S310F) exhibited constitutive autophosphorylation of HER2, as determined by western blotting. While these BEAS-2B cells were sensitive to neratinib, they were insensitive to erlotinib, a first-generation epidermal growth factor receptor-TKI. Neratinib also exerted anti-proliferative effects on -altered (H2170, Calu-3 and H1781) NSCLC cell lines. Neratinib was also demonstrated to exert strong tumor growth inhibitory activity in mouse xenograft models using -altered lung cancer cells. The results of the present study strongly suggest that neratinib has potential as a promising therapeutic option for the treatment of -altered NSCLC.

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