Inhibition of glucuronidation in pancreatic cancer improves gemcitabine anticancer activity

FRAUNHOFFER, NICOLAS ALEJANDRO; ABUELAFIA, ANALÍA MEILERMAN; CHANEZ, BRICE; BIGONNET, MARTIN; GAYET, ODILE; ROQUES, JULIE; CHULUYAN, EDUARDO; DUSETTI, NELSON; IOVANNA, JUAN

Cancer Communications

John Wiley and Sons Inc

Año: 2022 vol. 42 p. 1212 - 1216

Pancreatic ductal adenocarcinoma (PDAC) treatmentis focused on two regimens. The polychemotherapy,FOLFIRINOX (folinic acid, fluorouracil, irinotecan, oxali-platin), is used in patients with good health conditions, while gemcitabine, as monotherapy, in patients withpoor health conditions. Gemcitabine resistance-associated pathways have been targeted to sensitize cancercells, but the results were disappointing. Using a transcrip-tomic bioinformatics analysis combined with biologicalvalidation, we showed that glucuronidation was associ-ated with the gemcitabine resistance in PDAC, and itsinhibition could switch tumors from resistant to sensitive.