Targeting the epidermal growth factor receptor by erlotinib (Tarceva) for the treatment of esophageal cancer

Background & Aims: Esophageal cancer is the sixth most common cause of cancer-related death worldwide. Due to very poor 5-year-survival new therapeutic approaches are mandatory. Erlotinib (TarcevaTM), an inhibitor of epidermal growth factor receptor tyrosine kinase (EGFR-TK), potently suppresses the growth of various tumors, but its effect on esophageal carcinoma, known to express EGFR, remains unexplored. We therefore studied the antineoplastic potency of erlotinib in human esophageal cancer cells.

Results: Erlotinib induced growth inhibition of the human esophageal squamous cell carcinoma (ESCC) cell lines Kyse–30, Kyse–70 and Kyse–140, and the esophageal adenocarcinoma cell line OE–33, as well as in primary cell cultures of human esophageal cancers. Combining erlotinib with cetuximab or the tyrphostin AG1024 resulted in additive or even synergistic antiproliferative effects. Erlotinib induced cell cycle arrest at the G1/S checkpoint. The erlotinib-mediated signaling involved the inactivation of EGFR-TK and ERK1/2, the upregulation of the cyclin-dependent kinase inhibitors p21Waf1/CIP1 and p27Kip1, and the downregulation of the cell cycle promoter cyclin D1. However, erlotinib induced neither cytotoxicity nor apoptosis in esophageal cancer cells.

Conclusion: The inhibition of EGFR-TK by erlotinib appears to be a promising novel approach for innovative treatment strategies of esophageal cancer, as it induced growth inhibition and cell cycle arrest in human esophageal cancer cells and enhanced the antineoplastic effects of other targeted agents.

Keywords: EGFR, apoptosis, cell cycle, esophageal cancer, growth inhibition, tyrosine kinase