Emerging Oncometabolites in Cancer Development and Progression

Dear Colleagues, 

The role of metabolic enzymes in normal cell development and growth is widely recognized. The deregulation of these metabolic enzymes is directly associated with the development, growth, and progression of cancer. Mutations such as loss- or gain-of-function in genes coding for metabolic enzymes signal for metabolic deregulation and foster cancer growth in different ways, one of which is via "oncometabolites”. 

Oncometabolites are metabolites whose accumulation in abnormal quantities causes deregulation of the metabolic pathway and other pathways associated with it, instigating cancerous transformation. Recent technological advancements have enabled the profiling of metabolites and oncometabolites whose accumulation is linked with tumor development and progression. In different cancers, the accumulation of oncometabolites is influenced by factors such as diet, gut microbiota, and metabolic capacity. These factors regulate the abundance of specific metabolites that may push the epigenetic regulation of genes involved in tumorigenesis. 

Currently, fumarate, succinate, and D-2-hydroxyglutarate (D-2HG) are widely recognized as oncometabolites. Increased accumulation of these metabolites is reported to cause cellular dysregulation, driving cellular transformation and oncogenesis. However, other metabolites in the tumor microenvironment, including lactate, need to be further explored to determine their roles as emerging oncometabolites. Technological advances in mass spectrometry, magnetic resonance imaging, multi-omics profiling, metabolic flux analyses, and mathematical modeling would be advantageous in this quest to discover unidentified oncometabolites in cancers. Studying oncometabolite accumulation in the tumor microenvironment will also improve our understanding of tumor innervation and cancer–nerve-cell crosstalk. Gaining comprehensive knowledge of the tumorigenic potential of emerging oncometabolites is of high clinical importance. 

Prof. Dr. Debabrata Banerjee
Dr. Deepshikha Mishra
Guest Editors

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