T Friess1, W Scheuer, M Hasmann. 1. Roche Diagnostics GmbH, Pharma Research Penzberg, Department of Pharmacology TR-PD2, Nonnenwald 2, D-82372 Penzberg, Germany. thomas.friess@roche.com
Abstract
BACKGROUND: The human epidermal growth factor receptors HER1/EGFR and HER2 offer potential targets for treating non-small cell lung cancer (NSCLC). The antitumor efficacy of erlotinib (Tarceva, F. Hoffmann-La Roche, Ltd., Basel, Switzerland), a HER1/EGFR tyrosine-kinase inhibitor, was investigated in relation to HER1/EGFR and HER2 expression in five NSCLC xenograft models. MATERIALS AND METHODS: Tumor-bearing mice were randomized to daily oral erlotinib, 50 mg/kg, or vehicle (controls) for 20-50 days. The antitumor efficacy of erlotinib was measured through tumor volume, serum tumor markers and tumor biomarkers. Tumor HER1/EGFR and HER2 expression were analyzed immunohistochemically. RESULTS: Erlotinib reduced tumor volume in three NSCLC models. It also reduced serum tumor marker levels and the extent of inhibition correlated with tumor growth inhibition. HER1/EGFR and HER2 expression differed between the five tumor models, suggesting that expression level does not predict response to treatment. CONCLUSION: Erlotinib showed differing antitumor activity in five NSCLC models, suggesting that its antitumor effect is independent of HER1/EGFR and HER2 overexpression.
BACKGROUND: The human epidermal growth factor receptors HER1/EGFR and HER2 offer potential targets for treating non-small cell lung cancer (NSCLC). The antitumor efficacy of erlotinib (Tarceva, F. Hoffmann-La Roche, Ltd., Basel, Switzerland), a HER1/EGFR tyrosine-kinase inhibitor, was investigated in relation to HER1/EGFR and HER2 expression in five NSCLC xenograft models. MATERIALS AND METHODS:Tumor-bearing mice were randomized to daily oral erlotinib, 50 mg/kg, or vehicle (controls) for 20-50 days. The antitumor efficacy of erlotinib was measured through tumor volume, serum tumor markers and tumor biomarkers. TumorHER1/EGFR and HER2 expression were analyzed immunohistochemically. RESULTS:Erlotinib reduced tumor volume in three NSCLC models. It also reduced serum tumor marker levels and the extent of inhibition correlated with tumor growth inhibition. HER1/EGFR and HER2 expression differed between the five tumor models, suggesting that expression level does not predict response to treatment. CONCLUSION:Erlotinib showed differing antitumor activity in five NSCLC models, suggesting that its antitumor effect is independent of HER1/EGFR and HER2 overexpression.
Authors: J Jason Clark; Matthew Provenzano; Henry R Diggelmann; Ningyong Xu; Skylar S Hansen; Marlan R Hansen Journal: Otol Neurotol Date: 2008-09 Impact factor: 2.311