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. 2021 Jun 3;11:656851. doi: 10.3389/fonc.2021.656851

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Copyright © 2021 Hipólito, Martins, Mendes, Lopes-Coelho and Serpa

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Targeting metabolic pathways as a putative strategy to tackle metastatic cancer. Glycolytic inhibitors have been shown as being a promising application for the treatment of metastatic cancer. The compound 2-deoxy-d-glucose (2-DG) acts as an inhibitor of hexokinase 2 (HK-2), while 3PO, 1-(4-pyridinyl)-3-(2-quinolinyl)-2-propen-1-one (PFK15) and ACT-PFK-158 were designed to inhibit the activity of PFKFB3. A modified version of lonidamine was developed to inhibit OXPHOS and mitochondrial bioenergetics. Mutations in isocitrate dehydrogenases 1/2 (IDH 1/2) leads to the generation of the oncometabolite 2-hydroxyglutarate (2-HG), being the development of IDH^mut inhibitors, as AGI-5027, AGI-5198, and AG-120, an attempt to abrogate 2-HG production. Moreover, omeprazole and orlistat, inhibitors of fatty acid synthase (FASN), showed a promising clinical applicability in the treatment of metastatic cancer.