Category

Archives

Therapeutic implication of HER2 in advanced biliary tract cancer

Currently, there is no validated therapeutic target for biliary tract cancer (BTC). This study aimed to investigate the pre-clinical and clinical implication of HER2 as a therapeutic target in BTC. We established two novel HER2-amplified BTC cell lines, SNU-2670 and SNU-2773, from gallbladder cancer patients. SNU-2670 and SNU-2773 cells were sensitive to trastuzumab, dacomitinib, and afatinib compared with nine HER2-negative BTC cell lines. Dacomitinib and afatinib led to G1 cell cycle arrest in SNU-2773 cells and apoptosis in SNU-2670 cells. Furthermore, dacomitinib, afatinib, and trastuzumab showed synergistic cytotoxicity when combined with some cytotoxic drugs including gemcitabine, cisplatin, paclitaxel, and 5-fluorouracil. In a SNU-2670 mouse xenograft model, trastuzumab demonstrated a good anti-tumor effect as a monotherapy and in combination with gemcitabine increasing apoptosis. In our clinical data, 13.0% of patients with advanced BTC were defined as HER2-positive. Of these, three patients completed HER2-targeted chemotherapy. Two of them demonstrated a partial response, and the other one showed stable disease for 18 weeks. In summary, these pre-clinical and clinical data suggest that HER2 could be a therapeutic target, and that a HER2-targeting strategy should be developed further in patients with HER2-positive advanced BTC.

Related Products

Cat.No. Product Name Information Publications Customer Product Validation
S2727 Dacomitinib (PF-00299804) Dacomitinib (PF299804, PF299) is a potent, irreversible pan-ErbB inhibitor, mostly to EGFR with IC50 of 6 nM in a cell-free assay. Dacomitinib inhibits ERBB2 and ERBB4 with IC50 of 45.7 nM and 73.7 nM, respectively. Dacomitinib is effective against NSCLCs with EGFR or ERBB2 mutations (resistant to gefitinib) as well as those harboring the EGFR T790M mutation. Dacomitinib inhibits cell growth and induces apoptosis. Phase 2. (58) (4)

Related Targets