Methotrexate update 2014: 70 years in autoimmunity and cancer treatment



Year of publication 2014
Type Article in Periodical
Magazine / Source Česko-slovenská pediatrie
MU Faculty or unit

Faculty of Medicine

Field Paediatry
Keywords methotrexate; autoimmunity; neoplasms; biological markers; toxicity; adverse effects
Description Immunosupressive and antineoplastic activity brought methotrexate to its clinical use many years ago. Although modern antitumour and antiinflammatory drugs and new antifolates have challenged methotrexate, its use in rheumatoid arthritis and in some types of pediatric and adult malignancies remains a gold standard. The principal main mechanism of action of methotrexate is competitive inhibition of dihydrofolate reductase. Recently, other pharmacodynamic effects have been described. Potent inflammation inducers such as leukotriene-B4 and polyamine synthesis were found to be reduced by methotrexate treatment. Jun N-terminal kinase and B cell lymphoma 2 gene are downregulated by methotrexate. Its metabolite, 7-hydroxymethotrexate and also its intracellular polyglutamated forms show a different spectrum of inhibitory activity as well as potency towards dihydrofolate reductase and other enzymes. In this review, we summarize recent information data on methotrexate in both fields of its use, oncology and rheumatology. We also discuss new biomarkers of toxicity for further improvement of therapeutic protocols.
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