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Cancer metabolism as a central driving force of glioma pathogenesis

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Abstract

The recent identification of distinct genetic and epigenetic features in each glioma entity is leading to a multilayered, integrated diagnostic approach combining histologic features with molecular genetic information. Somatic mutations in isocitrate dehydrogenase (IDH) and receptor tyrosine kinase (RTK) pathways are key oncogenic events in diffuse gliomas, including lower grade (grade II and III) gliomas (LGG) and the highly lethal brain tumor glioblastoma (GBM), respectively, where they reprogram the epigenome, transcriptome, and metabolome to drive tumor growth. However, the mechanisms by which these genetic aberrations are translated into the aggressive nature of gliomas through metabolic reprogramming have just begun to be unraveled. The intricate interactions between the oncogenic signaling and cancer metabolism have also been recently demonstrated. Here, we describe a set of recent discoveries on cancer metabolism driven by IDH mutation and mutations in RTK pathways, highlighting the integration of genetic mutations, metabolic reprogramming, and epigenetic shifts, potentially providing new therapeutic opportunities.

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Acknowledgments

This work is supported by the National Institute for Neurological Diseases and Stroke Grant NS73831; the Defeat GBM Research Collaborative, a subsidiary of National Brain Tumor Society, National Cancer Institute Grant CA119347; The Ben and Catherine Ivy Foundation; generous donations from the Ziering Family Foundation in memory of Sigi Ziering; and a grant provided by The Novartis Foundation (Japan) for the Promotion of Science, The Cell Science Research Foundation, a Grant-in-Aid from the Tokyo Biochemical Research Foundation, and JSPS KAKENHI Grant Number 15K19067.

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  1. Department of Pathology, Tokyo Women’s Medical University, Tokyo, 162-8666, Japan

    Kenta Masui

  2. Ludwig Institute for Cancer Research, University of California San Diego, La Jolla, CA, 92093, USA

    Webster K. Cavenee & Paul S. Mischel

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  1. Kenta Masui
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  2. Webster K. Cavenee
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Correspondence to Kenta Masui or Paul S. Mischel.

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Masui, K., Cavenee, W.K. & Mischel, P.S. Cancer metabolism as a central driving force of glioma pathogenesis. Brain Tumor Pathol 33, 161–168 (2016). https://doi.org/10.1007/s10014-016-0265-5

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