Driver mutations and differential sensitivity to targeted therapies: a new approach to the treatment of lung adenocarcinoma

Cancer Treat Rev. 2010 Nov:36 Suppl 3:S21-9. doi: 10.1016/S0305-7372(10)70016-5.

Abstract

The adenocarcinoma of the lung has recently shown peculiar molecular characteristics, which relate with both carcinogenesis and response to targeted drugs. Several molecular alterations have been defined as "driver mutations". These are responsible for both the initiation and maintenance of the malignancy. The epidermal growth factor receptor (EGFR) pathway is the main regulator of cell function and cancer development. It has a widely defined role in the occurrence of driver mutations. Up till now EGFR gene mutations, KRAS gene mutations and EML4-ALK fusion genes are the most widely recognized alterations involved in both the biology and the clinical management of lung adenocarcinoma. In this review we report the molecular bases that have led to the clinical application of the detection for such genetic impairments. Subsequently we discuss the clinical studies regarding the prognostic role and the predictive value for response to anti-EGFR tyrosine kinase inhibitors (TKI) of the same mutations. We also provide a potential algorithm as a guide in the choice of the best treatment for patients with adenocarcinoma.

Publication types

  • Review

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / genetics*
  • Algorithms
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • ErbB Receptors / genetics*
  • Gene Expression
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics*
  • Molecular Targeted Therapy / methods*
  • Mutation*
  • Oncogene Proteins, Fusion / genetics
  • Phosphatidylinositol 3-Kinases
  • Predictive Value of Tests
  • Prognosis
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins p21(ras)
  • Treatment Outcome
  • ras Proteins / genetics

Substances

  • EML4-ALK fusion protein, human
  • KRAS protein, human
  • Oncogene Proteins, Fusion
  • Proto-Oncogene Proteins
  • Phosphatidylinositol 3-Kinases
  • ErbB Receptors
  • Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins