Primers on molecular pathways: nuclear receptors in pancreatic cancer. The ligand-independent way

Nuclear receptors (NRs) are ligand-activated transcription factors that regulate gene expression. These receptors share a quite similar structure and mechanism of action. Upon ligand binding, NRs translocate from the cytoplasm to the nucleus and bind to specific DNA sequences that regulate expression of different genes. In the absence of ligand the cascade of signaling events is different and either activation or repression may occur. Interestingly, several NRs are implicated in the pathogenesis of pancreatic cancer (PanCa). Specifically, androgen and estrogen receptor-related pathways are active in patients with pancreatic tumors, thus representing a suitable target for PanCa treatment. Although anti-hormone treatment has a modest effect on PanCa, ligand-independent activation of NRs remains overall unexplored in this disease.