Treatment of non-small-cell lung cancer and pharmacogenomics: where we are and where we are going.
OBJECTIVE
This review highlights the numerous molecular biology findings in the field of lung cancer with potential therapeutic impact in both the near and distant future.


RESULTS
Abundant preclinical and clinical data indicate that BRCA1 mRNA expression is a differential modulator of chemotherapy sensitivity. Single nucleotide polymorphisms in the excision repair cross-complementing 1 gene (ERCC1) influence survival with cisplatin-based chemotherapy. For the first time, epidermal growth factor receptor (EGFR) mutations have been shown to predict dramatic responses in metastatic lung adenocarcinomas. The crosstalk between estrogen and EGFR pathways have also been revealed. MicroRNAs control the expression of cognate target genes and predict relapse in surgically resected non-small-cell lung cancer patients. Overexpression of the Wingless-type (Wnt) genes and methylation of Wnt antagonists have been documented in non-small-cell lung cancer.


CONCLUSIONS
Understanding the relevance of these findings can help to change the clinical practice in oncology towards customizing chemotherapy and targeted therapies, leading to improvement both in survival and in cost-effectiveness.
Rosell
Rafael
R
Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain. rrosell@ico.scs.es
Cuello
Mauricio
M
Cecere
Fabiana
F
Santarpia
Mariacarmela
M
Reguart
Noemi
N
Felip
Enriqueta
E
Taron
Miquel
M
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics; D004720:Endonucleases / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D019398:Genes, BRCA1; D052138:Genes, Neoplasm / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics; D009154:Mutation / Q000187:drug effects; D009363:Neoplasm Proteins / Q000187:drug effects / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000187:drug effects; D015854:Up-Regulation
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D004967:Estrogens; D009363:Neoplasm Proteins; D066246:ErbB Receptors; C071447:ERCC1 protein, human; D004720:Endonucleases