Abstract
Increasing the efficacy of anticancer agents and avoiding toxic effects is a critical issue in clinical oncology. Identifying biomarkers that predict clinical outcome would ensure improved patient care. Gemcitabine is widely used to treat various solid tumors as a single agent or in combination with other drugs. The therapeutic index of gemcitabine is narrow, and abnormal pharmacokinetics leading to changes in plasma exposure is a major cause of adverse effects. A number of biomarkers have been proposed to predict efficacy of gemcitabine, focusing on molecular determinants of response identified at the tumor level. Genetic and functional deregulations that affect the disposition of a drug could be the reason for life-threatening adverse effects or treatment failure. In particular, deregulation of cytidine deaminase, the enzyme responsible for detoxification of most nucleotide analogs, should be examined. Identifying and validating biomarkers for pharmacogenetic testing before administration of gemcitabine is a step towards personalized medicine.
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J. Ciccolini and N. André wrote the manuscript, and all the authors researched data to include in the manuscript, contributed to discussion of content for the article, reviewed and edited the manuscript before submission, and revised the manuscript in response to the peer-reviewers' comments.
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Ciccolini, J., Mercier, C., Dahan, L. et al. Integrating pharmacogenetics into gemcitabine dosing—time for a change?. Nat Rev Clin Oncol 8, 439–444 (2011). https://doi.org/10.1038/nrclinonc.2011.1
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DOI: https://doi.org/10.1038/nrclinonc.2011.1
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