EGFR inhibition in the treatment of non-small cell lung cancer

Research output: Contribution to journalReview article

27 Scopus citations

Abstract

(Table Presented) Epidermal growth factor receptor (EGFR) inhibitors have introduced the concept of targeted therapy to the treatment of non-small cell lung cancer (NSCLC). These agents appear most effective in patients with tumors that are highly dependent on EGFR signaling pathways, a population that disproportionately includes females, nonsmokers, individuals of East Asian origin, and patients with adenocarcinoma histology. Currently available EGFR-inhibiting drugs include the tyrosine kinase inhibitors (TKIs) erlotinib, gefitinib, and lapatinib, which are administered orally and interfere with the intracellular tyrosine kinase domain, and the monoclonal antibodies (mAbs) cetuximab and panitumumab, which are administered intravenously and interfere with extracellular ligand binding. While the use of EGFR TKIs as monotherapy prolongs survival in metastatic NSCLC, they have demonstrated no benefit when added to conventional, cytotoxic chemotherapy. In contrast, the anti-EGFR mAb cetuximab appears most effective when combined with chemotherapy or radiation. Despite dramatic initial responses to treatment in some cases, NSCLC eventually becomes resistant to EGFR inhibition. Possible mechanisms include secondary mutations that interfere with drug binding, oncogenic pathways driven by other receptor tyrosine kinases, and independent activity of downstream signaling molecules. Efforts to overcome such resistance include irreversibly binding EGFR TKIs, multi-targeted TKIs, and combinations with chemotherapy, radiation, and other targeted therapies.

Original languageEnglish (US)
Pages (from-to)359-372
Number of pages14
JournalDrug Development Research
Volume69
Issue number6
DOIs
StatePublished - Sep 1 2008

Keywords

  • Epidermal growth factor receptor
  • Monoclonal antibodies
  • Non-small cell lung cancer
  • Targeted therapy
  • Tyrosine kinase inhibitors

ASJC Scopus subject areas

  • Drug Discovery

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