Pasqualina Castaldo, Simona Magi, Annamaria Assunta Nasti, Sara Arcangeli, Vincenzo Lariccia, Nicola Alesi, Massimo Tocchini and Salvatore Amoroso Pages 278 - 286 ( 9 )
It is well known that interindividual variability can affect the response to many drugs in relation to age, gender, diet, and organ function. Pharmacogenomic studies have also documented that genetic polymorphisms can exert clinically significant effects in terms of drug resistance, efficacy and toxicity by modifying the expression of critical gene products (drug-metabolizing enzymes, transporters, and target molecules) as well as pharmacokinetic and pharmacodynamic parameters.
A growing body of in vitro and clinical evidence suggests that common polymorphisms in the folate gene pathway are associated with an altered response to methotrexate (MTX) in patients with malignancy and autoimmune disease. Such polymorphisms may also induce significant MTX toxicity requiring expensive monitoring and treatment. Although the available data are not conclusive, they suggest that in the future MTX pharmacogenetics could play a key role in clinical practice by improving and tailoring treatment. This review describes the genetic polymorphisms that significantly influence MTX resistance, efficacy, and toxicity.
DHFR, MTHFR, MTX efficacy, MTX pharmacogenetics, MTX polymorphisms, MTX toxicity, Pharmacogenomic studies, pharmacodynamic parameters, RCF1 mutations, ATP-binding cassette (ABC)
Department of Neuroscience, Unit of Pharmacology, School of Medicine, University “Politecnica delle Marche”, and Department of General Services “Azienda Ospedaliero- Universitaria Ospedali Riuniti”, Ancona, Italy Via Tronto 10/A, 60020 Torrette, Ancona, Italy.