Researchers at the University of California, Davis have discovered a compound that inhibits both cyclooxygenase-2 (COX-2) /soluble epoxide hydrolase (sEH) to improve effectiveness of chemotherapy while protecting normal tissue from cisplatin toxicity.
Cisplatin-based therapies, despite their toxicity, are used to treat most cancers due to their moderate effectiveness. Cisplatin-based-first line therapies, such as combination gemcitabine and cisplatin (GC), are often used due to higher response rates, however have associated increased toxicities. There is a need for more effective therapies that do not have higher levels of toxicity.
Researchers at the University of California, Davis have discovered a compound, PTUPB, that inhibits COX-2 and sEH and protects normal tissues from cisplatin toxicity during treatment. The compound was successfully tested in patient-derived xenograft mouse models to potentiate cisplatin and GC therapies, resulting in significantly reduced tumor growth compared with inhibitors selective to either pathway, either as single agents or in combination. The models also showed prolonged survival, with no additional toxicity compared to cisplatin alone. This makes PTUPB an attractive agent for further development as a combination chemotherapy compound.
chemotherapy, combination chemotherapy, cyclooxygenase-2, COX-2, soluble epoxide hydrolase, sEH, inhibitor, PTUPB, cisplatin, toxicity, gemcitabine and cisplatin, GC, cisplatin-based-first line therapies