title: Biomarkers in lung oncology.
abstract: The survival of advanced non-small-cell lung cancer patients is short in spite of advances in new combination chemotherapy regimens. The benefit of adding antiangiogenic drugs and/or EGFR inhibitors is unclear. For the vast majority of patients without EGFR mutations, treatment approaches based on customization should be pursued. BRCA1 is central to the repair of DNA damage and is an important modulator of the differential effect of chemotherapy. Retrospective and prospective data indicate that low BRCA1 mRNA levels predict better response and survival when patients are treated with cisplatin, non-taxane combinations. For an important subgroup of patients with EGFR mutations, selective treatment with EGFR tyrosine kinase inhibitors is a major advance, with a dramatic impact on clinical outcomes. In a prospective study of customized erlotinib [1], overall response rate was 70% (including 12% complete responses), median progression free survival was 14 months (even longer in women and in patients with del 19), 20% of patients were disease-free at three years, and median survival was 27 months. Nonetheless, these clinical outcomes fall short of curability and continuous treatment with erlotinib or gefitinib is required. It is plausible that several genetically defined subclasses of EGFR mutations could help to improve current clinical outcomes by combining erlotinib or gefitinib with other targeted drugs.
authors.affiliation: Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Badalona, Spain. rrosell@iconcologia.net
authors.forename: Rafael
authors.initials: R
authors.lastname: Rosell
authors.forename: Alain
authors.initials: A
authors.lastname: Vergnenegre
authors.forename: Baorui
authors.initials: B
authors.lastname: Liu
authors.forename: Manuel
authors.initials: M
authors.lastname: Cobo
authors.forename: Bartomeu
authors.initials: B
authors.lastname: Massuti
authors.forename: Jia
authors.initials: J
authors.lastname: Wei
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Molina
authors.forename: Carlota
authors.initials: C
authors.lastname: Costa
authors.forename: Cristina
authors.initials: C
authors.lastname: Queralt
authors.forename: Miquel
authors.initials: M
authors.lastname: Taron
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D019313:BRCA1 Protein / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000378:metabolism* / Q000556:secondary; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004720:Endonucleases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D009154:Mutation; D057285:Precision Medicine; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D066246:ErbB Receptors; C071447:ERCC1 protein, human; D004720:Endonucleases