Oncometabolism
[2] The Warburg Effect, which describes how cancer cells change their metabolism to become more oncogenic in order to proliferate and eventually invade other tissues in a process known as metastasis.
[4] In the 1920s, Otto Heinrich Warburg discovered an intriguing bioenergetic phenotype shared by most tumor cells: a higher-than-normal reliance on lactic acid fermentation for energy generation.
[14] These defects cause an overabundance of endogenous metabolites, which are frequently involved in critical epigenetic changes and signaling pathways that have a direct impact on cancer cell metabolism.
Several mechanisms have been linked to D-2-hydroxyglutarate, succinate, and fumarate with the inhibition of α-KG–dependent dioxygenases, this causes epigenetic changes that affect the expression of genes involved in cell differentiation and the development of malignant characteristics.
[27] The group of Timothy A. Chan[28] described a mechanism by which abnormal accumulation of the oncometabolite D-2-hydroxyglutarate in brain tumor samples increased DNA methylation, a process that has been shown to play a key role in oncogenesis.
[29] On the other hand, in paraganglioma cells, succinate and fumarate were found to methylate histones, effectively silencing the genes PNMT and KRT19, which are involved in neuroendocrine differentiation and epithelial-mesenchymal transition, respectively.
The discovery of new therapeutic and reliable markers that exploit vulnerabilities of cancer cells, are being used to targeting either upstream or downstream effectors of these pathways.
[15] Oncometabolites can be used as diagnostic biomarkers and may be able to assist oncologists in making more precise decisions in early stages of tumorigenesis, particularly in predicting more aggressive tumor behavior.
[32] Therefore, limiting the supply of D-2-hydroxyglutarate by inhibiting the detected mutant IDH enzymes could be a good therapeutical approach to IDH-mutant cancers.
[33] IHC staining has been shown to be a useful diagnostic tool for prioritizing patients for SDH mutation testing in early stages of cancer.
[41] Metabolights is an open-access database for metabolomics research that collects all experimental data from leading journals' metabolic experiments.
These proteins appear to be involved in oncometabolism and targeting and uncoupling BRD4 actions in carcinogenic cells, as well as stopping pro-migratory signals and changing cytokine metabolism, particularly IL-6.
