thymidylate synthase targeting therapy in HER2 positive breast cancer

氟尿嘧啶(5-FU)是治疗乳腺癌的关键药物。胸苷合成酶(TS)的过度表达使其对5-FU产生耐药。研究人员已报道TS的表达受PI3K/Akt/mTOR途径的调控，并研究了TS靶向治疗以增强5-FU的抗肿瘤作用。在体外，曲妥珠单抗和拉帕替尼可抑制SkBr3中TS的表达和转录，并增强5-FU的抗肿瘤作用。然而，在初代和获得性曲妥珠单抗耐药的乳腺癌细胞株中，HER2靶向治疗对TS没有抑制作用，这是通过上调PI3K/Akt/mTOR信号和Of HER2内化来实现的。研究人员得出结论，TS抑制疗法对曲妥珠单抗敏感的HER2阳性乳腺癌有效。除了上述发现，我们还发现含有HER2的二聚体是HER2靶向治疗的一个新的预测因子，并在乳腺癌委员会上发表了报告。

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.