thymidylate synthase targeting therapy in HER2 positive breast cancer

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Fluoropyrimidine (5-FU) is key drug in treatment of breast cancer. Overexpression of thymidylate synthase (TS) confers resistant to 5-FU. The researchers have reported that TS expression is regulated by PI3K/Akt/mTOR pathway and have investigated TS targeting therapy to enhance antitumor effect of 5-FU therapy. In vitro, trastuzumab and lapatinib inhibited TS expression and transcription, and enhanced anti-tumor effect of 5-FU in SkBr3. However, in de-novo and acquired trastuzumab-resistant breast cancer cell lines showed no suppression of TS by HER2-targeting therapy, which was conferred by upregulation of PI3K/Akt/mTOR signaling and ofHER2-internalization. The researchers concluded that TS-inhibition therapy is effective in trastuzumab-sensitive HER2 positive breast cancer. Besides above findings, we found HER2-containing dimer as a novel predictive factor of HER2-targeting therapy and reported in breast cancer committees.