O-247 Molecular mechanisms of sensitivity and resistance to the HER1/EGFR-tyrosine kinase inhibitor erlotinib (Tarceva™)

Restoring E-Cadherin Expression Increases Sensitivity to Epidermal Growth Factor Receptor Inhibitors in Lung Cancer Cell Lines

“…These data are consistent with the finding that E-cadherin expression is lost when a NSCLC cell line becomes erlotinibresistant after exposing it to increasing levels of erlotinib (24). Our results suggest that E-cadherin expression would be a clinically relevant biomarker for a patient's selection of EGFR TKI therapy and responsiveness to EGFR TKIs.…”

Dual mitogen-activated protein kinase and epidermal growth factor receptor inhibition in biliary and pancreatic cancer

“…The genes identified were genes involved in very specific cellular functions, such as growth factor-growth factor receptor interactions, signal transduction, angiogenesis, and cell cycle regulation, which represent potential pathways to escape from EGFR blockade. Preliminary reports from similar studies in other tumor types that compare the gene expression in cells, in which resistance to the drug has been induced by prolonged drug exposure, have actually identified some of the genes here described, such as the platelet-derived growth factor receptor and fibroblast growth factor receptor genes (41). It is possible that this list of relevant genes can be further reduced by expanding the number of cell lines tested using more strict criteria to select the key genes, excluding inducible genes, by combining the expression profiles before and after exposure to the drug, and by combining data from cell with intrinsic and acquired resistance.…”

Therapeutic Inhibition of the Epidermal Growth Factor Receptor in High-Grade Gliomas: Where Do We Stand?

“…In view of these controversial data, a clear-cut evaluation of the significance of pMAPK or pAKT for the sensitivity of HER1/EGFR-expressing tumors toward HER1/EGFR TK inhibitors is difficult. Other molecules that have been shown to modulate sensitivity to erlotinib in nonglioma-derived cell lines are fibroblast growth factor receptor, platelet-derived growth factor receptor, E-, and H-cadherin (117,118).…”