title: Determinants of response and resistance to cytotoxics.
abstract: There is an underlying feeling in the oncology community that chemotherapy has reached a therapeutic "glass ceiling" in non-small cell lung cancer, and that we will never attain the acceptable survival rates that are just beyond our reach. Multiple clinical trials have tested doublets, triplets, and sequential chemotherapy in what is often regarded as a futile attempt to break through this ceiling. Recent large randomized trials have not shown that any of these combinations is superior to any of the others. Nevertheless, the analysis of DNA and RNA from patients' serum can permit us to assess genes that may be specific targets of certain cytotoxic agents and others that may be markers of multidrug resistance. With this information, we will hopefully be able to create guidelines for individualized chemotherapy. With this in mind, the Spanish Lung Cancer Group has designed a trial to test the involvement of various genes in resistance to gemcitabine and cisplatin. With the gene corral that will emerge from this trial, we will create an up-front diagnostic test for selecting the most appropriate gemcitabine plus cisplatin regimen for the treatment of non-small cell lung cancer.
authors.affiliation: Medical Oncology Service, Hospital Germans Trias i Pujol, Badalona, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Rosell
authors.forename: Mariano
authors.initials: M
authors.lastname: Monzó
authors.forename: Vicente
authors.initials: V
authors.lastname: Alberola
authors.forename: Miquel
authors.initials: M
authors.lastname: Taron
authors.forename: Agustin
authors.initials: A
authors.lastname: Barnadas
authors.forename: Jose Miguel
authors.initials: JM
authors.lastname: Sánchez
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Manzano
authors.forename: José Javier
authors.initials: JJ
authors.lastname: Sanchez
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000032:analysis; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage / Q000494:pharmacology; D004249:DNA Damage; D019175:DNA Methylation; D004273:DNA, Neoplasm; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic; D005819:Genetic Markers; D006801:Humans; D019656:Loss of Heterozygosity; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D011237:Predictive Value of Tests; D015398:Signal Transduction; D000093542:Gemcitabine
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D005819:Genetic Markers; D003841:Deoxycytidine; D002945:Cisplatin; D000093542:Gemcitabine