Optimization of genetics to create therapies for metastatic (stage IV) non-small-cell lung cancer.
BACKGROUND
Non-small-cell lung cancer (NSCLC) is a disseminated disease in 50% of cases, with a gloomy prognosis and median survivals of < 1 year.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Rosell
Rafael
R
Hospital Germans Trias i Pujol, Catalan Institute of Oncology, Medical Oncology Service, Ctra Canyet, s/n 08916 Badalona, Barcelona, Spain. rrosell@ico.scs.es
Moran
Teresa
T
Viteri
Santiago
S
Carcereny
Enric
E
Gasco
Amaya
A
Quiroga
Vanessa
V
Wei
Jia
J
Camps
Carlos
C
Massuti
Bartomeu
B
D019313:BRCA1 Protein / Q000032:analysis / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D002352:Carrier Proteins / Q000032:analysis; D017322:Clinical Trials, Phase II as Topic; D004268:DNA-Binding Proteins; D066246:ErbB Receptors / Q000235:genetics; D000069347:Erlotinib Hydrochloride; D056488:Histone Chaperones; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D009154:Mutation; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000032:analysis; D011799:Quinazolines / Q000627:therapeutic use; D012333:RNA, Messenger / Q000032:analysis
D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D056488:Histone Chaperones; D009687:Nuclear Proteins; D011799:Quinazolines; D012333:RNA, Messenger; C466234:UIMC1 protein, human; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors