The MK2/Hsp27 axis is a major survival mechanism for pancreatic ductal adenocarcinoma under genotoxic stress
Menée in vitro et à l'aide d'un modèle murin d'adénocarcinome canalaire du pancréas, cette étude met en évidence le rôle de la kinase MK2 et de la protéine de choc thermique Hsp27 dans la survie des cellules cancéreuses soumises à un stress génotoxique
Pancreatic ductal adenocarcinoma (PDAC) is frequently treated with combination chemotherapies, but resistance is common. Here, Grierson and colleagues studied resistance mechanisms to the combination of 5-fluorouracil, irinotecan, and oxaliplatin (FIRINOX), and identified a key pathway involving MAPK activated protein kinase 2 (MK2) and heat shock protein 27 (Hsp27). Targeting MK2 prevented activation of Hsp27 and increased tumor cell apoptosis in response to FIRINOX in vitro, and the combination of MK2 inhibition with FIRINOX suppressed tumor growth and prolonged animal survival in cell line–derived xenografts and an autochthonous mouse model of PDAC, without additional toxicity. These studies suggest that MK2 inhibition might improve the efficacy of FIRINOX-based regimens in patients with PDAC.