EGFR-mutated lung cancer: a paradigm of molecular oncology

Oncotarget. 2010 Nov;1(7):497-514. doi: 10.18632/oncotarget.186.

Abstract

The development of EGFR tyrosine kinase inhibitors for clinical use in non-small cell lung cancer and the subsequent discovery of activating EGFR mutations have led to an explosion of knowledge in the fields of EGFR biology, targeted therapeutics and lung cancer research. EGFR-mutated adenocarcinoma of the lung has clearly emerged as a unique clinical entity necessitating the routine introduction of molecular diagnostics into our current diagnostic algorithms and leading to the evidence-based preferential usage of EGFR-targeted agents for patients with EGFR-mutant lung cancers. This review will summarize our current understanding of the functional role of activating mutations, key downstream signaling pathways and regulatory mechanisms, pivotal primary and acquired resistance mechanisms, structure-function relationships and ultimately the incorporation of molecular diagnostics and small molecule EGFR tyrosine kinase inhibitors into our current treatment paradigms.

Keywords: EGFR; lung cancer; oncology; therapy; tyrosine kinase.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use
  • Carcinoma / diagnosis*
  • Carcinoma / drug therapy
  • Carcinoma / genetics*
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / genetics*
  • ErbB Receptors / metabolism
  • Humans
  • Lung Neoplasms / diagnosis
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics*
  • Medical Oncology / methods
  • Medical Oncology / standards
  • Models, Biological
  • Molecular Diagnostic Techniques* / methods
  • Molecular Diagnostic Techniques* / standards
  • Molecular Targeted Therapy / methods*
  • Mutant Proteins / genetics
  • Mutant Proteins / metabolism
  • Protein Kinase Inhibitors / therapeutic use

Substances

  • Antineoplastic Agents
  • Mutant Proteins
  • Protein Kinase Inhibitors
  • EGFR protein, human
  • ErbB Receptors