Development and clinical indications of cetuximab

R. Labianca, N. La Verde, Marina Chiara Garassino

Research output: Contribution to journalArticlepeer-review

Abstract

Cetuximab is a chimeric immunoglobulin G1 monoclonal antibody that targets the extracellular domain of the epidermal growth factor receptor (EGFR) with high specificity and affinity. it competitively inhibits endogenous ligand binding and thereby inhibits subsequent EGFR activation. The EGFR signaling pathways regulate cell differentiation, proliferation, migration, angiogenesis and apoptosis, all of which become deregulated in cancer cells. EGFR is an important target for cancer therapy and many studies have demonstrated that cetuximab is active in several types of cancer, particularly colorectal and head and neck cancer. Cetuximab enhances the effects of many standard cytotoxic agents, including irinotecan, and in combination with chemotherapy it can elicit antitumor responses in tumors that previously failed to respond to that chemotherapy. Cetuximab also enhances radiation-induced apoptosis. On the basis of a pivotal European randomized study (the BOND study) and of 2 clinical studies conducted in the USA, cetuximab has been approved in combination with irinotecan for patients affected by EGFR-expressing metastatic colon cancer after failure with irinotecan. There have only been a few small phase II trials on first-line treatment in metastatic colorectal cancer, but the results suggest promising activity of cetuximab together with irinotecan or oxaliplatin. There is some evidence that additive efficacy can be achieved using EGFR inhibitors in combination with vascular endothelial growth factor receptor inhibitors such as bevacizumab. A correlation between response and the main toxicity (acne-like skin reaction) has been observed but is unclear. EGFR status as a specific marker for EGFR inhibitors is controversial. At the moment, EGFR expression does not appear to be a predictive factor for response to EGFR inhibitors.

Original languageEnglish
JournalInternational Journal of Biological Markers
Volume22
Issue number1 SUPPL. 4
Publication statusPublished - Jan 2007

Keywords

  • Cetuximab
  • Colorectal cancer
  • EGFR

ASJC Scopus subject areas

  • Biochemistry
  • Immunology

Fingerprint Dive into the research topics of 'Development and clinical indications of cetuximab'. Together they form a unique fingerprint.

Cite this