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• W2133010487 endingPage "2829" @default.
• W2133010487 startingPage "2811" @default.
• W2133010487 abstract "Gemcitabine is one of the most widely used pyrimidine analogues, with a well-established role as a first- and second-line treatment of several types of tumors. Several preclinical and clinical studies have been done to obtain information on molecular determinants of gemcitabine activity and metabolism, in order to predict whether this drug will be effective and safe for the individual patient. Among these molecular determinants, the mRNA and protein expression of equilibrative transporter-1 (ENT1) and ribonucleotide reductase (RR) emerged as possible predictors of drug activity in studies on pancreatic and non-small cell lung cancer. However, cytidine deaminase polymorphisms and activity were correlated with clinical outcome and severe toxicities, whereas further studies should evaluate both P53 dependent and independent pathways involved in gemcitabine induced apoptosis. Improved knowledge on these determinants is critical for the optimal development of combination of gemcitabine with other conventional or biological therapies, as well as to exploit the radiosensitizing potential of gemcitabine. Emerging technologies such as massive parallel sequencing, gene expression arrays and proteomics may identify novel biomarkers in tumor material, while polymorphisms and phenotyping analysis should unravel factors involved in drug toxicity. Validation of these markers in preclinical models should be used for the appropriate patient enrolment into subsequent prospective studies. Hopefully, novel pharmacogenetic biomarkers will be validated in these prospective studies and used to select cancer patients to be treated with gemcitabine-based regimens in the near future or to enroll them in studies with prodrugs in order to bypass resistance mechanisms. Keywords: Gemcitabine, pharmacogenetics, equilibrative transporter-1, cytidine deaminase, drug combination, radiosensitization, polymorphisms, ribonucleotide reductase (RR), biomarkers, prodrugs" @default.
• W2133010487 created "2016-06-24" @default.
• W2133010487 creator A5035296183 @default.
• W2133010487 creator A5041229832 @default.
• W2133010487 creator A5042640895 @default.
• W2133010487 date "2012-05-01" @default.
• W2133010487 modified "2023-10-16" @default.
• W2133010487 title "Molecular Targets of Gemcitabine Action: Rationale for Development of Novel Drugs and Drug Combinations" @default.
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