Cancer metabolism as a central driving force of glioma pathogenesis.
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.
Department of Pathology, Tokyo Women's Medical University, Tokyo, 162-8666, Japan. masui-kn@research.twmu.ac.jp.
Kenta
K
Masui
Ludwig Institute for Cancer Research, University of California San Diego, La Jolla, CA, 92093, USA.
Webster K
WK
Cavenee
Ludwig Institute for Cancer Research, University of California San Diego, La Jolla, CA, 92093, USA. pmischel@ucsd.edu.
Paul S
PS
Mischel
D001932:Brain Neoplasms / Q000209:etiology* / Q000378:metabolism* / Q000628:therapy; D044127:Epigenesis, Genetic; D005910:Glioma / Q000209:etiology* / Q000378:metabolism*; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics / Q000502:physiology; D058990:Molecular Targeted Therapy; D009154:Mutation; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology
D007521:Isocitrate Dehydrogenase; D020794:Receptor Protein-Tyrosine Kinases
Genetic-metabolism interaction; Glioma; IDH; Metabolic reprogramming; Molecular genetics; RTK