Dihydropyrimidine dehydrogenase in the metabolism of the anticancer drugs

Abstract

Cancer caused by fundamental defects in cell cycle regulation leads to uncontrolled growth of cells. In spite of the treatment with chemotherapeutic agents of varying nature, multiple resistance mechanisms are identified in cancer cells. Similarly, numerous variations, which decrease the metabolism of chemotherapeutics agents and thereby increasing the toxicity of anticancer drugs have been identified. 5-Fluorouracil (5-FU) is an anticancer drug widely used to treat many cancers in the human body. Its broad targeting range is based upon its capacity to act as a uracil analogue, thereby disrupting RNA and DNA synthesis. Dihydropyrimidine dehydrogenase (DPD) is an enzyme majorly involved in the metabolism of pyrimidines in the human body and has the same metabolising effect on 5-FU, a pyrimidine analogue. Multiple mutations in the DPD gene have been linked to 5-FU toxicity and inadequate dosages. DPD inhibitors have also been used to inhibit excessive degradation of 5-FU for meeting appropriate dosage requirements. This article focusses on the role of dihydropyrimidine dehydrogenase in the metabolism of the anticancer drug 5-FU and other associated drugs.