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Fig. 1 | Bioresources and Bioprocessing

Fig. 1

From: Leveraging and manufacturing in vitro multicellular spheroid-based tumor cell model as a preclinical tool for translating dysregulated tumor metabolism into clinical targets and biomarkers

Fig. 1

Schematic diagram of targeted metabolic pathways in cancer therapy. Through the regulation of various signaling pathways, the metabolism of cancer cells changes compared with normal cells. Therefore, targeting tumor metabolic pathways is an important direction for anticancer treatment. The accumulation of mannose-6-phosphate (M-6-P) impairs further glucose metabolism. Tumor cells with low level of mannose phosphate isomerase (PMI) are sensitive to mannose, which can also become sensitive to mannose by siRNA-targeted PMI (Gonzalez et al. 2018). Glycolysis breaks down glucose into pyruvate and produces a variety of intermediates into the pentose phosphate pathway, TCA cycle, lipid metabolism, and amino acid metabolism. The pentose phosphate pathway provides reducing equivalents and precursors for nucleotide synthesis. In addition to energy metabolism, the TCA cycle also provides precursors for lipid and amino acid synthesis. Acetyl-coA is an important intermediate of energy metabolism. In human brain tumors, the contribution of acetate oxidation to the acetyl-coA pool is enhanced, and acetyl-coA synthetase 2 (ACSS2) is highly expressed, which can be a potential target for tumor detection and treatment (Mashimo et al. 2014). Acetyl-CoA carboxylase (ACC) and malonyl-CoA decarboxylase (MCD) are key enzymes in the fatty acid synthetic pathway, catalyzing the interconversion of acetyl-CoA and malonyl-CoA. At present, anticancer drugs targeting ACC have been applied in clinics, and siRNA inhibition of MCD is adverse to cancer cells, which makes MCD a potential therapeutic target (Currie et al. 2013). 2-HG, a metabolite of mIDH (mutated isocitrate dehydrogenase) tumors, has become a useful prognostic cancer marker (Salamanca-Cardona et al. 2017). 2-HG inhibits branched chain amino acid transaminases (BCATs) activity, which increases glutamate from glutamine catalyzed by glutaminase (GLS). Therefore, anticancer drugs targeting mIDH and targeting GLS can be used in combination therapy (McBrayer et al. 2018). Arginine succinic acid synthase (ASS1) and asparagine synthase (ASNS) cannot be expressed in some tumor tissues, which can also become potential targets for cancer detection and treatment (Ananieva 2015). Target metabolic enzymes (Blue); Anticancer drugs (Red); Potential targets (Green); Tumor biomarkers (Orange). Up arrow and down arrow denote the increased and decreased level of metabolites or enzymes, respectively

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