Repositioning mifepristone as leukaemia inhibitory factor receptor antagonist for the treatment of pancreatic adenocarcinoma

Abstract

Pancreatic cancer is leading cause of cancer mortality and is projected to become the second cause of cancer mortality in the next decade. While gene wide association studies and next generation sequencing analyses have identified molecular patterns and transcriptome profiles with prognostic relevance, therapeutic opportunities remain limited. Among the genes that were upregulated in pancreatic ductal adenocarcinomas (PDAC) the leukaemia inhibitory factor (LIF) has emerged as potential therapeutic candidate. Since there are no LIFR antagonists available for clinical use, we have developed an in-silico strategy to identify potential LIFR antagonists and drug reposition as LIFR antagonists. The results of these studies allowed the identification of mifepristone, a progesterone/glucocorticoid antagonist, clinical used in medical abortion, as potent LIFR antagonist