Trametinib Potentiates Anti-PD-1 Efficacy in Tumors Established from Chemotherapy-Primed Pancreatic Cancer Cells.

ABSTRACT: Despite advances in immune checkpoint inhibitors, chemotherapy remains the standard therapy for patients with pancreatic ductal adenocarcinoma (PDAC). As the combinations of chemotherapy, including the FOLFIRINOX [5-fluorouracil, F; irinotecan, I; and oxaliplatin, O (FIO)] regimen, and immune checkpoint inhibitors have failed to demonstrate clinical benefit in patients with metastatic PDAC tumors, there is increasing interest in identifying therapeutic approaches to potentiate ICI efficacy in patients with PDAC. In this study, we report that neoadjuvant FOLFIRINOX-treated human PDAC tumors exhibit increased MEK/ERK activation. We also show elevated MEK/ERK signaling in ex vivo PDAC slice cultures and cell lines treated with a combination of FIO. In addition, we find that the KPC-FIO cells,

SUBMITTER: Pham TD 

PROVIDER: S-EPMC11614707 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature