Correlation of TP with the efficacy of capecitabine

High expression of thymidine phosphorylase (TP) is associated with poor prognosis in patients with colorectal cancer.Tokunaga et al. found that immunohistochemical staining for TP in surgically resected specimens of colorectal cancer correlated TP expression with histological differentiation, lymph node metastasis, lymphatic infiltration, vascular infiltration, and tumor grade. And patients with negative TP in tumor tissues had higher postoperative survival rates than those with positive TP. Nozawa, Yasuno et al. further showed that TP expression in tumor cells and stromal cells had different roles, and patients with TP production by tumor cells had a poor prognosis, while those with TP production by stromal cells in the mesenchyme were mainly involved in the local immune response and had a better prognosis. Haraguchi et al. studied the relationship between metastasis and TP in colorectal cancer and found that the TP content in tumor tissues was not related to metastasis or not, while the TP content in serum taken from peripheral veins of metastatic patients was significantly higher. Nishina measured TP and DPD protein levels in tumor tissues and found that the TP/DPD ratio was significantly higher in the chemotherapy-sensitive group than in the non-responsive group, and that patients with high TP/DPD ratios had significantly higher chemotherapy sensitivity and longer survival. Capecitabine is a new generation of oral fluoropyrimidines that are rapidly absorbed in the gastrointestinal tract as prodrugs. Thymidine phosphorylase (TP) is the last enzyme in the activation process of capecitabine, and TP concentration is higher in tumor tissues, especially in colorectal, gastric and breast cancers than in normal tissues. Therefore, more capecitabine can be converted to 5-Fu in cancer tissues, while there is less chance in normal tissues, thus avoiding the damage of 5-Fu to normal tissues, so the anti-tumor activity of capecitabine is high and the systemic toxicity is light. Retrospective studies suggest that high levels of TP expression are positively correlated with the clinical effectiveness of capecitabine, so the determination of intracellular TP concentration in tumor cells can be used as a predictor of the therapeutic effect of capecitabine. Some medical centers apply capecitabine for advanced colorectal cancer with high TP and 5-Fu for those with low TP.