Dihydropyrimidine dehydrogenase and its role in predictive oncology

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Klin Onkol 2003; 16(5): 219-222.

Summary: Fluoropyrimidine chemotherapeutics headed by 5-fluorouracil are used for the treatment of cancer since half of the last century. Though 5-fluorouracil (5-FU) is mainly used drug in the therapy of colorectal cancer, only 15 – 30 % of patiens are responsive to this treatment and some of them could suffer from severe toxicity. The understanding of 5-FU metabolism led to detection of enzymes limiting 5-FU bioefficiency. These resistence predictors could be followed-up before beginning of the cure to determine positive cure reaction probability or to enable to dispose another chemotherapy if the probability of cure response is weak. Dihydropyrimidine dehydrogenase (DPD) which participates in 5-FU catabolism is one of these predictors. DPD is present in normal and cancer cells, its expression is higher in normal cells. High DPD activity in tumour cells causes 5-FU inactivation before the cytotoxic effect of chemotherapeutics could exert. On the other side, DPD deficiency could result in development of life-threatening toxicity.

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