Critical update and emerging trends in epidermal growth factor receptor targeting in cancer

José Baselga, Carlos L. Arteaga

Research output: Contribution to journalReview article

618 Citations (Scopus)

Abstract

The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase of the ErbB receptor family that is abnormally activated in many epithelial tumors. The aberrant activation of the EGFR leads to enhanced proliferation and other tumor-promoting activities, which provide a strong rationale to target this receptor family. There are two classes of anti-EGFR agents: monoclonal antibodies (MAbs) directed at the extracellular domain of the receptor and small molecule, adenosine triphosphate-competitive inhibitors of the receptor's tyrosine kinase. Anti-EGFR MAbs have shown antitumor activity in advanced colorectal carcinoma, squamous cell carcinomas of the head and neck, non-small-cell lung cancer (NSCLC) and renal cell carcinomas. The tyrosine kinase inhibitors (TKIs) have a partially different activity profile. They are active against NSCLC, and a specific EGFR inhibitor has shown improvement in survival. Recently, mutations and amplifications of the EGFR gene have been identified in NSCLC and predict for enhanced sensitivity to anti-EGFR TKIs. In addition to specific anti-EGFR TKIs, there are broader acting inhibitors such as dual EGFR HER-2 inhibitors and combined anti-pan-ErbB and antivascular endothelial growth factor receptor inhibitors. Current research efforts are directed at selecting the optimal dose and schedule and identifying predictive factors of response and resistance beyond EGFR gene mutations and/or amplifications. Finally, there is a need for improved strategies to integrate anti-EGFR agents with conventional therapies and to explore combinations with other molecular targeted approaches including other antireceptor therapies, receptor-downstream signaling transduction inhibitors, and targeted approaches interfering with other essential drivers of cancer, such as angiogenesis.

Original languageEnglish (US)
Pages (from-to)2445-2459
Number of pages15
JournalJournal of Clinical Oncology
Volume23
Issue number11
DOIs
StatePublished - Dec 1 2005

Fingerprint

Epidermal Growth Factor Receptor
Neoplasms
Non-Small Cell Lung Carcinoma
Protein-Tyrosine Kinases
erbB-1 Genes
Receptor Protein-Tyrosine Kinases
Monoclonal Antibodies
Mutation
Vascular Endothelial Growth Factor Receptor
R Factors
Renal Cell Carcinoma
Squamous Cell Carcinoma
Colorectal Neoplasms
Appointments and Schedules
Adenosine Triphosphate
Therapeutics
Research

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Critical update and emerging trends in epidermal growth factor receptor targeting in cancer. / Baselga, José; Arteaga, Carlos L.

In: Journal of Clinical Oncology, Vol. 23, No. 11, 01.12.2005, p. 2445-2459.

Research output: Contribution to journalReview article

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