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World J Stem Cells. Aug 26, 2022; 14(8): 587-598
Published online Aug 26, 2022. doi: 10.4252/wjsc.v14.i8.587
Metabolic determinants of stemness in medulloblastoma
Paula Martín-Rubio, Pilar Espiau-Romera, Alba Royo-García, Laia Caja, Patricia Sancho
Paula Martín-Rubio, Pilar Espiau-Romera, Alba Royo-García, Patricia Sancho, Hospital Universitario Miguel Servet, IIS Aragón, Zaragoza 50009, Spain
Laia Caja, Department of Medical Biochemistry and Microbiology, Biomedical Center, Uppsala University, Uppsala SE-751, Sweden
Author contributions: Martín-Rubio P, Espiau-Romera P, Royo García A, Caja L, and Sancho P drafted the manuscript; Caja L and Sancho P designed the study and wrote the final version of the manuscript; Martín-Rubio P designed the figures; All authors approved the final version of the manuscript.
Supported by the Miguel Servet and pFIS fellowships, No. CP16/00121 (P.S.) and No. FI21/00031 (P.E-R.) from the Instituto de Salud Carlos III and cofinanced by European funds (FSE: “el FSE invierte en tu futuro”); Magnus Bergvalls Stiftelse, No. 2021-04284 (L.C.); and the IV Grant for Childhood Cancer Research from Asociación de Padres de Niños con Cáncer de Aragón (ASPANOA, P.S.).
Conflict-of-interest statement: There are no conflicts of interest to report.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Patricia Sancho, PhD, Senior Researcher, Hospital Universitario Miguel Servet, IIS Aragón, 1-3 Avda Isabel la Católica, Zaragoza 50009, Spain. psancho@iisaragon.es
Received: April 7, 2022
Peer-review started: April 7, 2022
First decision: May 11, 2022
Revised: May 26, 2022
Accepted: July 31, 2022
Article in press: July 31, 2022
Published online: August 26, 2022
Abstract

Medulloblastomas (MBs) are the most prevalent brain tumours in children. They are classified as grade IV, the highest in malignancy, with about 30% metastatic tumours at the time of diagnosis. Cancer stem cells (CSCs) are a small subset of tumour cells that can initiate and support tumour growth. In MB, CSCs contribute to tumour initiation, metastasis, and therapy resistance. Metabolic differences among the different MB groups have started to emerge. Sonic hedgehog tumours show enriched lipid and nucleic acid metabolism pathways, whereas Group 3 MBs upregulate glycolysis, gluconeogenesis, glutamine anabolism, and glutathione-mediated anti-oxidant pathways. Such differences impact the clinical behaviour of MB tumours and can be exploited therapeutically. In this review, we summarise the existing knowledge about metabolic rewiring in MB, with a particular focus on MB-CSCs. Finally, we highlight some of the emerging metabolism-based therapeutic strategies for MB.

Keywords: Medulloblastoma, Cancer stem cells, Stemness, Metabolism, Glycolysis, Lipids

Core Tip: Considering the profound cellular metabolism rewiring associated with the tumorigenesis process, metabolic targeting for cancer treatment has gained a lot of attention in the last years. Interestingly, increasing evidence indicates that cancer stem cells (CSCs) show unique metabolic features within tumours. A deeper understanding of the metabolic vulnerabilities of medulloblastoma (MB) and MB-CSCs would accelerate the design of novel therapeutic strategies with the aim of improving the survival of paediatric patients suffering this disease.