|Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
|Outline of Final Research Achievements
HER2-targeting agent lapatinib plus the oral fluoropyrimidine, capecitabine, is an effective treatment option for trastuzumab-refractory HER2-positive metastatic breast cancer. This study indicates that lapatinib has a synergistic antitumor effect with capecitabine from downregulation of TS which is mediated by the major transcription factor E2F1. We showed not only the molecular mechanism of lapatinib and capecitabine, but also possibility of the interaction between lapatinib and gemcitabine or anthracyclines from the result of downregulation of RRM1 and TOP2A by lapatinib. Our findings provide a rationale for clinical evaluation of combination chemotherapy with lapatinib and gemcitabine for breast cancer with HER2 amplification.