Pancreatic Ductal Adenocarcinoma: New Insights into the Actions of Vitamin A

Abstract

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.

Vitamin Nutritional Status in Patients with Pancreatic Cancer: A Narrative Review

“…Older studies report a lack of vitamin A in patients with PaC both associated with carcinomas in metastatic form, which then cause malabsorption [51] and pancreatic carcinoid syndrome [52]. A recent review evaluated the dysregulation of the functions of vitamin A (retinol) and its metabolites (retinoids) in PDAC and described their actions to support the development of new therapies and increase patient survival [53]. However, multiple factors, including nutritional components and individual-specific variable patterns, may play a role but are not exclusive predictors of PaC progression.…”

Levels of retinol and retinoic acid in pancreatic cancer, type-2 diabetes and chronic pancreatitis

“…This suggests a possible important role of ATRA in ADM (ref. 17,19 ). b) Pancreatic stellate cells (PSCs) -the retinol storing mesenchymal-like cells -have been described as an important part of the PDAC stroma interplay.…”

Chronicle of a discovery: the retinoic acid receptor

“…It is also used 'off label' for nonsmall cell lung cancer and breast cancer (Esteva et al 2003, Dragnev et al 2007. In addition, a recent phase 1 clinical trial has shown that at-RA is a potent stromal targeting agent in pancreatic cancer and is now entering phase 2 status (Kocher et al 2020, Mere Del Aguila et al 2022.…”