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Eur Rev Med Pharmacol Sci. 2012 Mar;16(3):285-98.

Genetic variants influencing fluoropyrimidine based-therapy and available methods to detect them.

Author information

1
Hematology-Oncology and Stem Cell transplantation Unit, National Cancer Institute, Fondazione "G. Pascale" IRCCS, Naples, Italy. rdifrancia@iapharmagen.org

Abstract

BACKGROUND:

Many clinicians acknowledge the importance of genetics in drug response and are favourable about using genetic tests to guide therapy. The 5-Fluorouracil (5-FU) is the backbone of different regimens for the treatment of several solid tumours. Unlikely, some patients develop gastrointestinal and hematologic toxicities when treated by the 5-FU, leading to the suspension of therapy. Current evidences of pharmacogenomics, have reported different polymorphisms associated to genes involved with fluoropyrimidine biotransformation. A multitude of methods has been applied to assess the mutational status of these genes, without defining a golden standard for the daily diagnostic routine, so far.

AIMS:

Some adverse drug response due to the administration of 5-FU can be predicted through pharmacogenomics testing tools. This report reviews the recent findings on the polymorphism for genes that are involved in the biotransformation of the drug and its association with the toxic effect in patients receiving 5-FU in mono o polychemoterapy. Most common fluoropyrimidines-based regimens are finely described. Also, we will take in considerations the recent methods used to identify these genetic alterations.

CONCLUSION:

Recent and evolving technological advances for genotyping will result in personalized treatment. In the next future the oncologists will have new means based on the genetic composition of the individual, to make treatment decisions for their patients maximizing benefit and minimizing toxicity. Based on these purpose, clinician and lab manager may join together to evaluate advantages and limitation, in terms of costs and applicability, of the most appropriate methods to set molecular diagnostics of 5-FU pharmacogenomics tests.

PMID:
22530343
[Indexed for MEDLINE]

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