Dihydropyrimidine dehydrogenase activity correlates with fluorouracil sensitivity in breast cancer

Yu Z., Yang Q., Sun J., Zhen J.

The fluoropyrimidine drug fluorouracil (FU) is one of the most frequently prescribed chemotherapeutic drugs for the curative and palliative treatment of various cancer patients. The identification of biological factors associated with tumors either responsiveness or resistance to FU chemotherapy, including FU, is increasingly being recognized as an important field of clinical cancer research. Aim: to analyze the relationship between intra-tumoral dihydropyrimidine dehydrogenase (DPD) level and FU chemosensitivity, as DPD is the initial and rate-limiting enzyme in the catabolism of FU. Materials and Methods: The histoculture drug response assay (HDRA) was performed for 54 patients. DPD expression was examined in 81 tumor samples from breast cancer patients received two cycles of FU-based primary chemotherapy before operation. Results: We found that intra-tumoral DPD enzyme activity was inversely correlated with FU cytotoxicity. We also revealed that low DPD expression was correlated with clinical response to FU-based primary chemotherapy. Conclusions: Our study indicated that DPD is a promising molecular maker for identifying tumor cells sensitivity in breast cancer patients receiving FU-based chemotherapy.

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