BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a gland-forming malignancy arising in the pancreas. It is estimated that in developed countries the incidence of PDAC will continue to rise, and PDAC is now the fourth leading cause of cancer-related deaths in the USA. The mortality of PDAC patients closely parallels the incidence rate, as this malignancy generally remains asymptomatic until it reaches an advanced stage. SUMMARY: The poor prognosis results from the aggressive nature of the tumor, late detection, and resistance to chemotherapy and radiotherapy. Retinoids, vitamin A (retinol) and its metabolites, such as retinoic acid (RA), play critical roles in important biological functions, including cell growth and differentiation, development, metabolism, and immunity. The actions of retinoids in maintaining normal pancreatic functions have generated considerable research interest from investigators interested in understanding and treating PDAC. Altered expression of retinoid receptors and other RA signaling pathway genes in human cancers offers opportunities for target discovery, drug design, and personalized medicine for distinct molecular retinoid subtypes. KEY MESSAGES: The goals of this review are to explore the potential activities of retinoids in the pancreas, to assess the evidence that retinoid functions become dysregulated in PDAC, and to describe the actions of retinoids in new therapies developed to increase patient survival.
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a gland-forming malignancy arising in the pancreas. It is estimated that in developed countries the incidence of PDAC will continue to rise, and PDAC is now the fourth leading cause of cancer-related deaths in the USA. The mortality of PDAC patients closely parallels the incidence rate, as this malignancy generally remains asymptomatic until it reaches an advanced stage. SUMMARY: The poor prognosis results from the aggressive nature of the tumor, late detection, and resistance to chemotherapy and radiotherapy. Retinoids, vitamin A (retinol) and its metabolites, such as retinoic acid (RA), play critical roles in important biological functions, including cell growth and differentiation, development, metabolism, and immunity. The actions of retinoids in maintaining normal pancreatic functions have generated considerable research interest from investigators interested in understanding and treating PDAC. Altered expression of retinoid receptors and other RA signaling pathway genes in human cancers offers opportunities for target discovery, drug design, and personalized medicine for distinct molecular retinoid subtypes. KEY MESSAGES: The goals of this review are to explore the potential activities of retinoids in the pancreas, to assess the evidence that retinoid functions become dysregulated in PDAC, and to describe the actions of retinoids in new therapies developed to increase patient survival.
Authors: Thierry Conroy; Françoise Desseigne; Marc Ychou; Olivier Bouché; Rosine Guimbaud; Yves Bécouarn; Antoine Adenis; Jean-Luc Raoul; Sophie Gourgou-Bourgade; Christelle de la Fouchardière; Jaafar Bennouna; Jean-Baptiste Bachet; Faiza Khemissa-Akouz; Denis Péré-Vergé; Catherine Delbaldo; Eric Assenat; Bruno Chauffert; Pierre Michel; Christine Montoto-Grillot; Michel Ducreux Journal: N Engl J Med Date: 2011-05-12 Impact factor: 91.245
Authors: Pierre-Jacques Brun; Ambar Grijalva; Richard Rausch; Elizabeth Watson; Jason J Yuen; Bhaskar C Das; Koichi Shudo; Hiroyuki Kagechika; Rudolph L Leibel; William S Blaner Journal: FASEB J Date: 2014-11-11 Impact factor: 5.191
Authors: Donghui Li; Hongwei Tang; Manal M Hassan; Elizabeth A Holly; Paige M Bracci; Debra T Silverman Journal: Cancer Causes Control Date: 2010-11-21 Impact factor: 2.506
Authors: Ayush Sharma; Thomas C Smyrk; Michael J Levy; Mark A Topazian; Suresh T Chari Journal: Gastroenterology Date: 2018-04-30 Impact factor: 22.682