Phosphorylated epidermal growth factor receptor on tumor-associated endothelial cells is a primary target for therapy with tyrosine kinase inhibitors.

摘要: We determined whether phosphorylated epidermal growth factor receptor (EGFR) expressed on tumor-associated endothelial cells is a primary target for therapy with EGFR tyrosine kinase inhibitors (TKIs). Human colon cancer SW620CE2 (parental) that do not express or human 2 (HER2) but transforming α (TGF-α) were transduced lentivirus carrying nontargeting small hairpin RNA (shRNA) TGF-α shRNA. The cell lines implanted into the cecum of nude mice. Two weeks later, treatment began saline, 4-[R]-phenethylamino-6-[hydroxyl] phenyl-7H-pyrrolo [2,3-d]-pyrimidine (PKI166), irinotecan. Endothelial in parental and shRNA tumors EGFR. Therapy PKI166 alone irinotecan produced apoptosis these necrosis EGFR-negative tumors. did EGFR, resistant to PKI166. response neoplasms antagonists has been correlated mutations, HER2 expression, Akt activation, gene copy number. Our present data using suggest expression by tumor leading activation major determinant susceptibility specific EGFR-TKI.