A. Scalvini et al., Investigation of MTHFR, DPYD, and TSER polymorphisms in 5-FU toxicity: a case report

5-Fluorouracil (5-FU) is a chemotherapic drug belonging to the fluoropyrimidine family, broadly used either alone or in combination with other agents. 5-FU indications include palliative and adjuvant treatment of many cancers, including colorectal, breast, head and neck cancers. 5-FU requires enzymatic conversion to the nucleotide floxouridine monophosphate (FdUMP) in order to exert its cytotoxic activity. The interaction between the FdUMP and the thymidylate synthase (TS) blocks the synthesis of thymidine triphosphate. The folate cofactor 5-10 methylenetetrahydrofolate (MTHF) and FdUMP form a covalently bound complex with TS. It should be underline that the MTHF intracellular levels are regulated by the enzyme MTHFR (MethyleneTetraHydroFolate Reductase). Enzymes involved in the 5-FU mechanism of action as well as those involved in its metabolism have shown polymorphisms at the genetic level, that influence the structure and function of the encoded protein.
Based on this, it has been suggested that the presence of polymorphisms could be one of the reason for the significant interindividual variability in the safety profile reported in patients undergoing 5-FU therapy. Thus, the knowledge of the 5-FU-related pharmacogenomic profile may help to predict the response outcome and the chemotherapy toxicity in patients treatedwith this drug. In this work, we described a case report of two patients with relevant systemic toxicity following 5-FU therapy.
The 5-FU related pharmacogenomic profile revealed polymorphisms in the target genes that may explain the clinical findings.

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