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Metabolites
Special Issues
Metabolism and Metabolic Targeting of Neuroblastoma
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Metabolism and Metabolic Targeting of Neuroblastoma

A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Endocrinology and Clinical Metabolic Research".

Deadline for manuscript submissions: closed (30 September 2023) | Viewed by 2928

Special Issue Editors

Dr. Sepideh Aminzadeh-Gohari

E-Mail Website
Guest Editor
Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, University Hospital of the Paracelsus Medical University, 5020 Salzburg, Austria
Interests: cancer; metabolism; neuroblastoma
Prof. Dr. Barbara Kofler

E-Mail Website
Guest Editor
Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, Paracelsus Medical University, 5020 Salzburg, Austria
Interests: metabolism; mitochondria; cancer; neuroblastoma; dietary intervention
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Neuroblastoma is one of the most common pediatric cancers that remains incurable in about 50% of children in high-risk stages despite aggressive multimodal treatment strategies. Even when patients survive, they usually have a high morbidity due to the side effects of intensive therapies, and are at risk of tumor recurrence.

Alterations in metabolic pathways such as glycolysis, mitochondrial respiration and lipid as well as amino acid metabolism are recognized hallmarks of neuroblastoma that contribute to tumor progression and interact with the tumor microenvironment, influencing the response and resistance to therapies.

Therefore, therapeutics targeting different facets of tumor metabolism are considered new and effective options to improve the efficacy of standard cancer therapies such as chemo-, radio-, and immunotherapy, and to mitigate the side effects of such therapies. This Special Issue of Metabolites presents the latest research on metabolism in neuroblastoma and therapeutic options in this area.

Dr. Sepideh Aminzadeh-Gohari
Prof. Dr. Barbara Kofler
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Metabolites is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • neuroblastoma
  • tumor metabolism
  • glycolysis
  • mitochondrial metabolism
  • tumor microenvironment
  • metabolic targeting of neuroblastoma
  • therapy response and resistance
  • multimodal therapy
  • lipid metabolism
  • amino acid metabolism

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Published Papers (1 paper)

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Research

20 pages, 4007 KiB  
Article
Triple Therapy with Metformin, Ketogenic Diet, and Metronomic Cyclophosphamide Reduced Tumor Growth in MYCN-Amplified Neuroblastoma Xenografts
by Luca Catalano, Sepideh Aminzadeh-Gohari, Daniela D. Weber, Rodolphe Poupardin, Victoria E. Stefan, William J. Smiles, Julia Tevini, René G. Feichtinger, Sophia Derdak, Martin Bilban, Stefan Bareswill, Markus M. Heimesaat and Barbara Kofler
Metabolites 2023, 13(8), 910; https://doi.org/10.3390/metabo13080910 - 3 Aug 2023
Cited by 1 | Viewed by 2262
Abstract
Neuroblastoma (NB) is a childhood cancer in which amplification of the MYCN gene is the most acknowledged marker of poor prognosis. MYCN-amplified NB cells rely on both glycolysis and mitochondrial oxidative phosphorylation (OXPHOS) for energy production. Previously, we demonstrated that a ketogenic diet [...] Read more.
Neuroblastoma (NB) is a childhood cancer in which amplification of the MYCN gene is the most acknowledged marker of poor prognosis. MYCN-amplified NB cells rely on both glycolysis and mitochondrial oxidative phosphorylation (OXPHOS) for energy production. Previously, we demonstrated that a ketogenic diet (KD) combined with metronomic cyclophosphamide (CP) delayed tumor growth in MYCN-amplified NB xenografts. The anti-diabetic drug metformin (MET) also targets complex I of the OXPHOS system. Therefore, MET-induced disruptions of mitochondrial respiration may enhance the anti-tumor effect of CP when combined with a KD. In this study, we found that MET decreased cell proliferation and mitochondrial respiration in MYCN-amplified NB cell lines, while the combination of KD, MET, and low-dose CP (triple therapy) also reduced tumor growth and improved survival in vivo in MYCN-amplified NB xenografts. Gene ontology enrichment analysis revealed that this triple therapy had the greatest effect on the transcription of genes involved in fatty acid ß-oxidation, which was supported by the increased protein expression of CPT1A, a key mitochondrial fatty acid transporter. We suspect that alterations to ß-oxidation alongside the inhibition of complex I may hamper mitochondrial energy production, thus explaining these augmented anti-tumor effects, suggesting that the combination of MET and KD is an effective adjuvant therapy to CP in MYCN-amplified NB xenografts. Full article
(This article belongs to the Special Issue Metabolism and Metabolic Targeting of Neuroblastoma)
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