Cetuximab enhances the anti-proliferative effect of trastuzumab in ERBB2 over-expressing breast cancer cells--preliminary study

Klin Onkol. 2011;24(5):356-60.

Abstract

Background: The tyrosine kinase receptor comprises a subclass of cell surface growth factor receptors. Inhibition of certain members of the Epidermal Growth Factor Receptor (EGFR) family is an effective treatment approach in some cancers. The anti-tumor effects are greater when this approach is combined with inhibition of the ERBB2 receptors. These studies provide novel experimental data demonstrating a significant augmentation of the anti-proliferative effects of monoclonal antibodies (cetuximab and trastuzumab) on human breast carcinoma cell lines with different level of ERBB receptor expression.

Materials and methods: Three breast cancer cell lines, MCF-7, BT-474, and SK-BR-3 were used. These are characterised by different levels of EGFR and/or other ERBB family members. Inhibition of cell growth in response to cetuximab, trastuzumab or their combination was assessed by MTT assay.

Results: The breast cancer cell lines differed in their sensitivity toTZ, CTX and their combination. The SK-BR-3 cancer cell line was sensitive to TZ. On the other hand, CTX had no effect on BT-474 or on SK-BR-3 that expressed low levels of EGFR and high levels of ERBB2.

Conclusion: Our new experimental data show that the combination of anti-EGF receptor and anti-ERBB2 mAb may inhibit cancer cells expressing both EGF and ERBB2 receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / pharmacology*
  • Antibodies, Monoclonal, Humanized / pharmacology*
  • Antineoplastic Agents / pharmacology*
  • Blotting, Western
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Line, Tumor / drug effects
  • Cell Proliferation / drug effects*
  • Cetuximab
  • Epidermal Growth Factor / metabolism
  • Female
  • Humans
  • Receptor, ErbB-2 / antagonists & inhibitors
  • Receptor, ErbB-2 / metabolism*
  • Trastuzumab

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Epidermal Growth Factor
  • Receptor, ErbB-2
  • Trastuzumab
  • Cetuximab