Erlotinib antitumor activity in non-small cell lung cancer models is independent of HER1 and HER2 overexpression

Anticancer Res. 2006 Sep-Oct;26(5A):3505-12.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Disease Models, Animal*
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / metabolism*
  • Erlotinib Hydrochloride
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Protein Kinase Inhibitors / therapeutic use*
  • Quinazolines / therapeutic use*
  • Receptor, ErbB-2 / metabolism*
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Quinazolines
  • Erlotinib Hydrochloride
  • ErbB Receptors
  • Receptor, ErbB-2