Multidisciplinary therapy using molecular targeting therapy and surgery for HER2/FGFR2-positive gastric cancer

2016 Fiscal Year Final Research Report

• Project/Area Number: 26462003
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Aichi Cancer Center Research Institute
• Principal Investigator: Ito Yuichi 愛知県がんセンター(研究所), 分子腫瘍学部, 研究員 (80397463)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: HER2陽性胃がん / FGFR2陽性胃がん / 細胞株パネル / ハーセプチン耐性株 / 耐性機構 / T-DM1 / 分子標的薬

Outline of Final Research Achievements

Among various types of gastric cancers, HER2-positive cancer proved to be effective target by trastuzumab (Tmab), but Tmab resistance remains a major problem to be resolved. In this study, we newly developed gastric cancer cell line panel including HER2 high/low gene amplified- and Tmab resistant cell lines and examined anti-tumor effect of T-DM1, Afatinib, an irreversible TKI and Tmab plus chemotherapy in mouse xenograft models. The results showed that T-DM1 and Afatinib alone and Tmab-paclitaxel combination exhibited significant anti-tumor effect against Tmab-resistant cell lines through different molecular mechanisms. In addition, we developed FGFR2 gene-amplified gastric scirrhous cancer cells and examined the effect of a new TKI for FGFR2 (PD173074), showing significant anti-tumor effect against FGFR2-positive cells. These results suggest a new treatment modality consisting of molecular targeting therapies and surgery against HER2-positive and FGFR2-positive gastric cancers.

Free Research Field

医歯薬学