title: Nuclear receptors and pathogenesis of pancreatic cancer.
abstract: Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with a median overall survival time of 5 mo and the five years survival less than 5%, a rate essentially unchanged over the course of the years. A well defined progression model of accumulation of genetic alterations ranging from single point mutations to gross chromosomal abnormalities has been introduced to describe the origin of this disease. However, due to the its subtle nature and concurring events PDAC cure remains elusive. Nuclear receptors (NR) are members of a large superfamily of evolutionarily conserved ligand-regulated DNA-binding transcription factors functionally involved in important cellular functions ranging from regulation of metabolism, to growth and development. Given the nature of their ligands, NR are very tempting drug targets and their pharmacological modulation has been widely exploited for the treatment of metabolic and inflammatory diseases. There are now clear evidences that both classical ligand-activated and orphan NR are involved in the pathogenesis of PDAC from its very early stages; nonetheless many aspects of their role are not fully understood. The purpose of this review is to highlight the striking connections that link peroxisome proliferator activated receptors, retinoic acid receptors, retinoid X receptor, androgen receptor, estrogen receptors and the orphan NR Nur, chicken ovalbumin upstream promoter transcription factor II and the liver receptor homologue-1 receptor to PDAC development, connections that could lead to the identification of novel therapies for this disease.
authors.affiliation: Simone Polvani, Mirko Tarocchi, Sara Tempesti, Andrea Galli, Department of Experimental and Clinical Biomedical Sciences, University of Florence, 50134 Florence, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Polvani
authors.affiliation: Simone Polvani, Mirko Tarocchi, Sara Tempesti, Andrea Galli, Department of Experimental and Clinical Biomedical Sciences, University of Florence, 50134 Florence, Italy.
authors.forename: Mirko
authors.initials: M
authors.lastname: Tarocchi
authors.affiliation: Simone Polvani, Mirko Tarocchi, Sara Tempesti, Andrea Galli, Department of Experimental and Clinical Biomedical Sciences, University of Florence, 50134 Florence, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Tempesti
authors.affiliation: Simone Polvani, Mirko Tarocchi, Sara Tempesti, Andrea Galli, Department of Experimental and Clinical Biomedical Sciences, University of Florence, 50134 Florence, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Galli
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D006801:Humans; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D011379:Prognosis; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D014408:Biomarkers, Tumor; D018160:Receptors, Cytoplasmic and Nuclear
keywords: COUP-TFII; Nuclear receptors; Nuclear receptors 2F2; Nuclear receptors 4A2; Orphan nuclear receptor; Pancreatic cancer; Pancreatic intraepithelial neoplasia; Peroxisome proliferator activated receptor; Retinoid X receptor; Testicular receptor 3