The ErbB2 receptor tyrosine kinase is overexpressed in approximately 30% of breast tumor cases and its overexpression correlates with an unfavorable prognosis. A major contributor for this course of the disease is the insensitivity of these tumors toward chemotherapy. Monoclonal antibodies, inhibiting the ligand-induced activation of the receptor and… (More)
FIGURE 11. Model for the inhibition of ErbB2 signaling by peptide aptamers. ErbB2 interacting peptide aptamers isolated by yeast two-hybrid screening analysis were introduced into cancer cells by infection with a lentiviral vector (A) or by direct transduction of a recombinantly produced aptamer protein (B). Within the cell, peptide aptamer AII-7 was able to interact with the ErbB2 receptor, inhibiting selected signaling functions without binding to the ATP-binding site. Aptamer AII-7 binding to ErbB2 leads to a decrease in AKT phosphorylation on heregulin induction of the receptor dimer and increases the sensitivity of MCF7-her2 cells toward paclitaxel. Our results show that a treatment targeting the ErbB2 receptor with aptamers in combination with chemotherapy might become useful.