Optimization of genetics to create therapies for metastatic (stage IV) non-small-cell lung cancer

Expert Opin Pharmacother. 2010 Jul;11(10):1683-93. doi: 10.1517/14656566.2010.482101.

Abstract

Importance of the field: Non-small-cell lung cancer (NSCLC) is a disseminated disease in 50% of cases, with a gloomy prognosis and median survivals of < 1 year.

Areas covered in this review: Based on substantial advances, cancer biology insights and novel biotechnology tools, customized treatment provides hints that cisplatin-based treatment can be optimized in favorable subgroups of patients according to gene expression DNA repair profiles. In 2004, it was discovered that 10-15% of NSCLC can harbor a new class of EGFR mutation conferring specific sensitivity to EGFR tyrosine kinase inhibitors.

What the reader will gain: The homologous recombination pathway provides information for customizing cisplatin-based chemotherapy. BRCA1 plays a central role in this pathway that can be used in tailoring chemotherapy. Patient subgroups can obtain significant increases in progression-free survival. For EGFR lung-addicted cancers, treatment with EGFR tyrosine kinase inhibitors like erlotinib provide impressive improvement in progression-free survival--up to 14 months with significant enhanced survival.

Take home message: Customized chemotherapy based on BRCA1 models can contribute to demonstrating this approach's clinical relevance, and the implementation of EGFR mutation assessment is warranted to identify EGFR-addicted lung cancers with a different prognosis that could benefit from a specifically targeted therapy approach.

Publication types

  • Review

MeSH terms

  • BRCA1 Protein / analysis
  • BRCA1 Protein / genetics
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carrier Proteins / analysis
  • Clinical Trials, Phase II as Topic
  • DNA-Binding Proteins
  • ErbB Receptors / genetics
  • Erlotinib Hydrochloride
  • Histone Chaperones
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology
  • Mutation
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Nuclear Proteins / analysis
  • Quinazolines / therapeutic use
  • RNA, Messenger / analysis

Substances

  • BRCA1 Protein
  • BRCA1 protein, human
  • Carrier Proteins
  • DNA-Binding Proteins
  • Histone Chaperones
  • Nuclear Proteins
  • Quinazolines
  • RNA, Messenger
  • UIMC1 protein, human
  • Erlotinib Hydrochloride
  • ErbB Receptors