The HER protein is a transmembrane tyrosine kinase receptor and a member of the epidermal growth factor receptors (EGFRs) family. HER2 acts as an oncogene in carcinomas. In particular, HER2 acts as a prognostic factor. Especially, Poziotinib is a specific inhibitor of HER family kinases.
Poziotinib inhibits phosphorylation of the HER family and downstream signaling molecules and induces apoptosis and G1 arrest. It exerts synergistic effects with chemotherapeutic agents in both HER2 amplified and HER2 non-amplified gastric cancer cells. Therefore, Poziotinib may be useful for the treatment of HER2 amplified gastric cancer alone or in combination with chemotherapeutic agents.
Poziotinib effectively inhibits HER family kinases with IC50 values of 3.2, 5.3, and 23.5 nM for HER1/2/4, respectively. It shows more potent inhibitory activity against both EGFR and HER2 compared to other HER family tyrosine kinase inhibitors. In addition, Poziotinib has potent growth inhibitory activity against HER2 amplified gastric cancer cells when compared to other HER family TKIs.
Poziotinib specifically inhibits the growth of HER2 amplified cells (SNU216 and N87). Furthermore, Poziotinib potently inhibits the phosphorylation of the HER family and downstream proteins and induces apoptosis and G1 arrest. These results suggest that Poziotinib exerts significant antitumor activity. Moreover, Poziotinib induces apoptosis and G1 cell cycle arrest in HER2 amplified gastric cancer cells. Besides, Poziotinib inhibits phosphorylation of the HER family and their downstream signaling molecules in HER2 amplified gastric cancer cells.
All in all, Poziotinib exerts a synergistic effect when administered with chemotherapeutic agents in gastric cancer cells
Hyun-Jin Nam, et al. Antitumor activity of Poziotinib, an irreversible Pan-HER inhibitor, alone or in combination with cytotoxic chemotherapeutic agents in gastric cancer. Cancer Lett. 2011 Mar 28;302(2):155-65.