Language

English

Publication Date

9-23-2025

Journal

Trends in Molecular Medicine

DOI

10.1016/j.molmed.2025.08.005

PMID

40993020

Abstract

Oncogenic MYCN drives aggressive disease in many cancers including neuroblastoma (NB). Metabolic reprogramming is essential to support cancer cell homeostasis and survival under nutrient- and oxygen-deprived conditions. MYCN directly reprograms many nodes of tumor-intrinsic metabolism, which have significant repercussions on the cells of the tumor microenvironment (TME), resulting in complex intercellular metabolic circuits that contribute to the immunosuppressive microenvironment of NB. These metabolic circuits are also regulated by the organismal and cellular circadian clock and host diet to further impact the TME and NB oncogenesis. This review discusses the mechanisms by which MYCN regulates the metabolic crosstalk between tumor, TME, and host, and provides evidence that therapeutic targeting of MYCN-reprogrammed metabolism can improve patient outcomes.

Keywords

MYCN, metabolism, neuroblastoma, tumor microenvironment

Published Open-Access

yes

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