Metabolic reprogramming in cholangiocarcinoma

Raggi, C., Taddei, M. L., Rae, C. , Braconi, C. and Marra, F. (2022) Metabolic reprogramming in cholangiocarcinoma. Journal of Hepatology, 77(3), pp. 849-864. (doi: 10.1016/j.jhep.2022.04.038) (PMID:35594992)

Abstract

Metabolic reprogramming is a hallmark of cancer and allows tumor cells to meet the increased energy demands required for rapid proliferation, invasion, and metastasis. Indeed, many tumor cells acquire distinctive metabolic and bioenergetic features to survive under conditions of limited resources, mainly using alternative nutrients. Several recent studies have explored the metabolic plasticity of cancer cells with the aim to identify new druggable targets, and therapeutic strategies aimed to limit the access to nutrients have been successfully applied to the treatment of some tumors. Cholangiocarcinoma (CCA), a highly heterogeneous tumor, is the second most common form of primary liver cancer. It is characterized by resistance to chemotherapy and poor prognosis, with 5-year survival lower than 20%. Deregulation of metabolic pathways has been described during the onset and progression of CCA. Increased aerobic glycolysis and glutamine anaplerosis provide CCA cells with the ability to generate biosynthetic intermediates. Other metabolic alterations involving carbohydrates, amino acids and lipids have been shown to sustain cancer cell growth and dissemination. In this review, we discuss the complex metabolic rewiring taking place during CCA development, leading to unique nutrient addiction. The possible role of therapeutic interventions based on metabolic changes is also thoroughly discussed.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Rae, Dr Colin and Braconi, Dr Chiara
• Authors: Raggi, C., Taddei, M. L., Rae, C., Braconi, C., and Marra, F.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Journal of Hepatology
• Publisher: Elsevier
• ISSN: 0168-8278
• ISSN (Online): 1600-0641
• Published Online: 18 May 2022
• Copyright Holders: Copyright © 2022 European Association for the Study of the Liver
• First Published: First published in Journal of Hepatology 77(3): 849-864
• Publisher Policy: Reproduced in accordance with the publisher copyright policy