Dihydropyrimidine dehydrogenase activity correlates with fluorouracil sensitivity in breast cancer.
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.


OBJECTIVE
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.


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.
Yu
Z
Z
Department of Breast Surgery, the Second Affiliated Hospital of Shandong University, Ji'nan, Shandong Province, People's Republic of China. yzg@medmail.com.cn
Yang
Q
Q
Sun
J
J
Zhen
J
J
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology*; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000378:metabolism*; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use*; D006801:Humans; D007150:Immunohistochemistry
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D042943:Dihydrouracil Dehydrogenase (NADP); D005472:Fluorouracil