Her2-Targeted Therapy Induces Autophagy in Esophageal Adenocarcinoma Cells.

摘要: Esophageal adenocarcinoma (EAC) is a highly lethal cancer type with an overall poor survival rate. Twenty to thirty percent of EAC overexpress the human epidermal growth factor receptor 2 (Her2), transmembrane tyrosine kinase promoting cell and proliferation. Patients Her2 overexpressing breast gastroesophageal may benefit from inhibitors. Therapy resistance, however, well documented. Since autophagy, lysosome-dependent catabolic process, implicated in resistance mechanisms, we tested whether autophagy modulation influences inhibitor sensitivity EAC. Her2-positive OE19 cells showed induction autophagic flux upon treatment small molecule Lapatinib. Newly generated Lapatinib-resistant (OE19 LR) increased basal compared parental P) cells. Based on these results, if combining Lapatinib inhibitors might be beneficial. P significantly reduced viability double treatment, while LR were already sensitive inhibition alone. Additionally, status marker expression (LC3B p62) investigated treatment-naive patient cohort (n = 112) using immunohistochemistry. Here, no significant correlation between LC3B p62 was found. Our data show that Her2-directed therapy associated higher level, which not per se status. Therefore, propose contribute acquired Her2-targeted EAC, beneficial for patients.