PT  - JOURNAL ARTICLE
AU  - NAKATA, SUSUMU
AU  - FUJITA, MITSUGU
AU  - NAKANISHI, HAYAO
TI  - Efficacy of Afatinib and Lapatinib Against <em>HER2</em> Gene-amplified Trastuzumab-sensitive and -resistant Human Gastric Cancer Cells
AID  - 10.21873/anticanres.13797
DP  - 2019 Nov 01
TA  - Anticancer Research
PG  - 5927--5932
VI  - 39
IP  - 11
4099  - http://ar.iiarjournals.org/content/39/11/5927.short
4100  - http://ar.iiarjournals.org/content/39/11/5927.full
SO  - Anticancer Res2019 Nov 01; 39
AB  - Background/Aim: Trastuzumab is the only clinically approved targeted therapy for HER2 gene-amplified gastric cancer at present. However, the clinical significance of multi-targeting tyrosine kinase inhibitors (TKIs) in HER2-positive gastric cancer remains unclear. Materials and Methods: We examined the anti-tumor activity of lapatinib and afatinib, that are reversible and irreversible TKIs, in HER2 gene-amplified trastuzumab-sensitive and - resistant gastric cancer cells (GLM-1 and GLM-1HerR2) in vitro and in vivo. Results: Afatinib inhibited the growth of GLM-1 and GLM-1HerR2 cells in vitro more efficiently than lapatinib by inducing G1 cell-cycle arrest and apoptosis. Preclinical studies in mice revealed that afatinib inhibited growth of intraperitoneal GLM-1 and subcutaneous GLM-1HerR2 tumor more strongly than lapatinib. Afatinib was more effective than lapatinib in blocking PI3K/Akt and MAPK signaling in both GLM-1 and GLM-1HerR2 cells. Conclusion: Afatinib could be a potential new molecular-targeted therapy for trastuzumab-sensitive and trastuzumab-resistant HER2 gene-amplified gastric cancers.