Influence of genetic markers on survival in non-small cell lung cancer

摘要: Cisplatin or carboplatin is commonly used with gemcitabine, docetaxel, paclitaxel vinorelbine as chemotherapy doublets in the treatment of advanced non-small cell lung cancer. Several randomized trials have failed to identify major differences survival between any these doublets. This lack evidence for improvement regimen has created a tabula rasa which no more large should be conducted out including genetic analysis. Patients see their concern, and other considerations, such cost qualify life, are relegated lower positions. Genetic alterations related transcription-coupled repair pathway nucleotide excision system (TC-NER) revealed subset patients who resistant cisplatin. TC-NER involves genes that deficient rare inborn disorders Cockayne syndrome xeroderma pigmentosum. For long time, ERCC1 mRNA levels been known correlate DNA capacity various tissues. Levels cisplatin adducts peripheral blood buccal mucosa cells predict response, high chemoresistance ovarian cancer malignant lymphocytes from chronic lymphocytic leukemia. Moreover , some instances, expression correlated polymorphisms. Overexpression correlates poor gemcitabine/cisplatin-treated patients. An ongoing customized ERCC1-based trial established on this knowledge. control arm cisplatin/docetaxel combined gemcitabine according levels. To date, 80 included. At preclinical level, XPD each other, overexpression causes selective resistance human tumor lines. Some polymorphisms associated capacity. In our experience, time disease progression significantly higher Lys751Gln genotype (9.6 months) than those Lys751Lys (4.2 months; p = 0.03). Other involved parallel systems may well provide same information, indicating degree biological redundancy. The subunit M1 ribonucleotide reductase (RRM1) linked retrospective assessment. Preliminary findings indicate low RRM1 show longer survival. highlights possibilities individually tailored chemotherapy. However, treated cisplatin/vinorelbine, opposite effect observed. had progression. When docetaxel was added gemcitabine/cisplatin, also better Our status can help decide cisplatin/gemcitabine docetaxel/ TC-NER-dependent activity similar anticancer agents cause DNA-binding enzymes kill (topoisomerase inhibitors). least 50% harbor benefit treatment. Genes spindle formation, centrosome functions transport along microtubule tracks further information potential markers resistance.