Klin Farmakol Farm. 2004;18(3):149-152

Individualizace farmakoterapie inhibitory tymidylát syntázy u nádorů gastrointestinálního traktu

Miroslav Svoboda1, Ondřej Slabý2
1 Masarykův onkologický ústav, Brno
2 Přírodovědecká fakulta Masarykovy univerzity v Brně

Keywords: thymidylate synthase, fluoropyrimidine derivatives, antifolates, complex profiles of gene expression.

Published: December 31, 2004  Show citation

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Svoboda M, Slabý O. Individualizace farmakoterapie inhibitory tymidylát syntázy u nádorů gastrointestinálního traktu. Klin Farmakol Farm. 2004;18(3):149-152.

Inhibitory tymidylát syntázy (TS) jsou často používány při léčbě nádorových onemocnění. Léčiva s inhibičním účinkem na tymidylát syntázu lze rozdělit na dvě hlavní skupiny: fluoropyrimidinové deriváty a analoga kyseliny listové. Tyto inhibitory jednak ovlivňují enzymatickou aktivitu TS, jednak dochází k metabolizaci těchto inhibitorů různými enzymy. Interindi­viduální rozdíly v expresi a aktivitě TS a metabolizujících enzymů by mohly být využity při předpovědi rezistence na jednotlivá cytostatika. Získané znalosti o expresi a aktivitě jednotlivých enzymů by pak mohly být využity při navrhování cílené individuální protinádorové terapie.

Bohužel rezistenci na cytostatika ovlivňují stovky genů. Pro přesnou předpověď rezistence pravděpodobně nebude stačit stanovení několika markerů. Pro takovou předpověď bude zřejmě nutné rutinní zavedení metod pro sledování exprese desítek nebo stovek genů a jejich proteinových produktů.

THE INDIVIDUALISED PHARMACOTHERAPY OF GASTROINTESTINAL CANCER BASED ON THYMIDYLATE SYNTHASE INHIBITORS

The inhibitors of thymidylate synthase (TS) are frequently used as anticancer drugs. These drugs can be divided into two principal groups: the fluoropyrimidine derivatives and folic acid analogs. All these inhibitors change enzymatic activity of TS, and at the same time they are also metabolizeded by different enzymes. The interindividual differences in the expression and activity of TS and of other enzymes can be exploited in the design of targeted individual anticancer therapy.

Unfortunately the drug resistance is influenced by hundreds of genes. If we would like to predict the drug resistance, the determination of as little as several markers would not be probably efficient. The routine establishment of methods of screening expression of tens or hundreds of genes and their protein products will be probably necessary for such prediction.

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