Insight in the treatment for pancreatic adenocarcinoma: discovery of the semisynthetic bile alcohol steroidal agonist BAR502 as a potent leukemia inhibitory factor receptor antagonist
The leukemia inhibitory factor (LIF), is a cytokine belonging to IL-6 family, whose overexpression correlate with poor prognosis in on cancer patients. LIF signaling is mediate by its binding to the heterodimeric LIF receptor (LIFR) complex formed by the LIFR receptor and Gp13o, leading to JAK1/STAT3 activation. The JAK/STAT3 pathway is over-regulated in several type of tumors, including pancreatic ductal adenocarcinoma (PDAC). Bile acids are steroid molecules that modulates the expression/activity of membrane and nuclear receptors, including the Farnesoid-X-Receptor (FXR) and G Protein Bile Acid Activated Receptor (GPBAR)1). In this study we have investigated whether ligands to FXR and GPBAR1 modulate LIF/LIFR pathway in ductal pancreatic acinar cells (PDAC) and whether these receptors are expressed in neoplastic tissues from a cohort PDCA patients.