MicroRNAs are non-coding RNAs that can block mRNA translation and influence mRNA stability. Recent evidence indicates that miRNA variations can affect drug resistance, efficacy, and metabolism, opening new avenues of pharmacogenomics research. We investigated associations between polymorphisms in both miRNA-containing genomic regions (primary and precursor miRNA) and in genes related to miRNA biogenesis with clinical outcome in metastatic colorectal cancer (mCRC) patients treated with 5-fluorouracil and irinotecan (CPT-11). Eighteen single-nucleotide polymorphisms (SNPs) were analyzed in 61 patients. A significant association with tumor response and time to progression (TTP) was found for SNP rs7372209 in pri-miR26a-1 (P=0.041 and P=0.017, respectively). The genotypes CC and CT were favorable when compared with the TT variant genotype. In addition, SNP rs1834306, located in the pri-miR-100 gene, significantly correlated with a longer TTP (P=0.04). In the miRNA-biogenesis pathway, a trend was identified between SNP rs11077 in the exportin-5 gene and disease control rate (P=0.076). This study is the first to suggest a relationship between treatment outcome and SNPs in the miRNA-biogenesis machinery, in both primary and precursor miRNAs. Our results suggest that miRNA polymorphic variants might be useful predictors of clinical outcome in mCRC patients treated with 5-fluorouracil and CPT-11 combination.

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The purpose of this study was to develop a simple and sensitive CE-UV method to quantify erlotinib and metabolites in urine. Following liquid-liquid extraction, erlotinib, and metabolites were separated with a BGE whose composition was phosphate buffer (pH 2.5, 65 mM) with 0.5% Tween 20. The applied voltage was 22 kV, capillary temperature 25°C and the sample injection was performed in the hydrodynamic mode. All the analyses were carried out in a fused silica capillary with an internal diameter of 75 μm and a total length of 37 cm. The detection of target compounds was performed at 240 nm. The calibration was linear in the range 0.15-20 mg/L for erlotinib and metabolites. Inter-and intraday imprecision were less than 4%. This simple, sensitive, accurate, and cost-effective method can be used in routine clinical practice to monitor erlotinib concentrations in urine from nonsmall cell lung cancer patients.

A rapid, sensitive, and specific method was developed and validated using a nonaqueous-capillary electrophoresis method with TOF-MS for determination of sunitinib and N-desethyl sunitinib in human urine. In order to avoid ionic suppression a urine samples dilution with methanol 1:10 previous step was used. This was the only treatment step to urine samples before the injection. Despite this dilution of the urine, the detection limit was as low as 0.07 mg/L for sunitinib and 0.15 mg/L for N-desethyl sunitinib. Separation of compounds was achieved with a mixture of 5 mM ammonium formate in methanol. The calibration curves were linear over the range of 0.5-50.0 mg/L for the two analyzed compounds. The within-run and between-run precisions were within 5%, while the accuracy ranged from 96.0 to 100.4%. This method can be used in routine clinical practice to monitor sunitinib and N-desethyl sunitinib drugs in the urine of cancer patients treated with once daily administration.

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