Abstract:Primary thymic carcinoma is a rare tumor of the thymus gland. The role of chemotherapy in treating advanced thymic carcinoma is unclear. It has recently been reported that thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), and orotate phosphoribosyltransferase (OPRT) expression may be important factors when predicting the effectiveness of 5-fluorouracil-based chemotherapy (Kaira et al., 74:419-425, 2011). In this report, we describe three cases in which S-1 or S-1 combination treatment was given… Show more
“… 8,20 We previously reported successful S-1 treatment for refractory thymic carcinoma with high OPRT expression. 10 The anticancer activity of 5-FU has been reported to be closely related to the intratumoral expression of TS and DPD in lung cancer. 11 We have also hypothesized that strong OPRT expression may be a predictive biomarker for S-1 therapy.…”
Section: Resultsmentioning
confidence: 99%
“…There is no pathway related to OPRT in its mode of action. Overall, like in squamous lung cancer and thymic carcinoma, 10 when combined with TS inhibition, cancer tissue that have high OPRT protein expression have the potential to be treated with S-1 through the inhibition for RNA synthease. Figure 3.…”
Section: Resultsmentioning
confidence: 99%
“…However, an OPRT-related pathway that leads to RNA synthesis inhibition is also thought to be an important mechanism for S-1. 10-12 …”
Objective: Malignant pleural mesothelioma (MPM) is a rare and aggressive, treatment-resistant cancer. Pemetrexed, an inhibitor of thymidylate synthase (TS), is used worldwide for MPM as a first-line chemotherapy regimen. However, there is little consensus for a second-line chemotherapy. S-1, a highly effective dihydropyrimidine dehydrogenase (DPD)-inhibitory fluoropyrimidine, mainly acts via a TS inhibitory mechanism similar to pemetrexed. Orotate phosphoribosyltransferase (OPRT) is a key enzyme related to the first step activation of 5-fluorouracil (5-FU) for inhibiting RNA synthesis. We investigated 5-FU related-metabolism proteins, especially focusing on OPRT expression, in MPM Methods and Patients: Fifteen MPM patients who were diagnosed between July 2004 and December 2013 were enrolled. We examined the protein levels of 5-FU metabolism-related enzymes (TS, DPD, OPRT, and thymidine phosphorylase [TP]) in 14 cases Results: High TS, DPD, OPRT, and TP expressions were seen in 28.6%, 71.4%, 85.7%, and 35.7% of patients, respectively. We found that OPRT expression was extremely high in MPM tissue. We experienced one remarkable case of highly effective S-1 combined therapy for pemetrexed refractory MPM. This case also showed high OPRT protein expression Conclusion: The present study suggests that OPRT expression is high in MPM tumors. Although pemetrexed is mainly used for MPM chemotherapy as a TS inhibitor, S-1 has potential as an anticancer drug not only as a TS inhibitor but also inhibiting RNA synthesis through the OPRT pathway. This is the first report investigating OPRT protein expressions in MPM.
“… 8,20 We previously reported successful S-1 treatment for refractory thymic carcinoma with high OPRT expression. 10 The anticancer activity of 5-FU has been reported to be closely related to the intratumoral expression of TS and DPD in lung cancer. 11 We have also hypothesized that strong OPRT expression may be a predictive biomarker for S-1 therapy.…”
Section: Resultsmentioning
confidence: 99%
“…There is no pathway related to OPRT in its mode of action. Overall, like in squamous lung cancer and thymic carcinoma, 10 when combined with TS inhibition, cancer tissue that have high OPRT protein expression have the potential to be treated with S-1 through the inhibition for RNA synthease. Figure 3.…”
Section: Resultsmentioning
confidence: 99%
“…However, an OPRT-related pathway that leads to RNA synthesis inhibition is also thought to be an important mechanism for S-1. 10-12 …”
Objective: Malignant pleural mesothelioma (MPM) is a rare and aggressive, treatment-resistant cancer. Pemetrexed, an inhibitor of thymidylate synthase (TS), is used worldwide for MPM as a first-line chemotherapy regimen. However, there is little consensus for a second-line chemotherapy. S-1, a highly effective dihydropyrimidine dehydrogenase (DPD)-inhibitory fluoropyrimidine, mainly acts via a TS inhibitory mechanism similar to pemetrexed. Orotate phosphoribosyltransferase (OPRT) is a key enzyme related to the first step activation of 5-fluorouracil (5-FU) for inhibiting RNA synthesis. We investigated 5-FU related-metabolism proteins, especially focusing on OPRT expression, in MPM Methods and Patients: Fifteen MPM patients who were diagnosed between July 2004 and December 2013 were enrolled. We examined the protein levels of 5-FU metabolism-related enzymes (TS, DPD, OPRT, and thymidine phosphorylase [TP]) in 14 cases Results: High TS, DPD, OPRT, and TP expressions were seen in 28.6%, 71.4%, 85.7%, and 35.7% of patients, respectively. We found that OPRT expression was extremely high in MPM tissue. We experienced one remarkable case of highly effective S-1 combined therapy for pemetrexed refractory MPM. This case also showed high OPRT protein expression Conclusion: The present study suggests that OPRT expression is high in MPM tumors. Although pemetrexed is mainly used for MPM chemotherapy as a TS inhibitor, S-1 has potential as an anticancer drug not only as a TS inhibitor but also inhibiting RNA synthesis through the OPRT pathway. This is the first report investigating OPRT protein expressions in MPM.
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