Reprogramación metabólica de células tumorales y terapias dirigidas contra el fenotipo metabólico de estas células

Abstract

The studies done about the metabolic rewiring of the tumor cells conclude that these changes have two main objectives: to improve tumor cell survival and to aloe their growing in an acid and hypoxic medium with a low amount of nutrients. To this end, they have designed different processes that allow them to obtain energy quickly, to perform numerous biosynthetic reactions and to eliminate the elements that would induce their death. Tumor cells use the Warburg effect and their capacity to obtain nutrients from non-conventional sources. To obtain biosynthetic precursors, tumor cells use their high ability to capture glucose and glutamine. To survive in an adverse environment, they inhibit apoptotic pathways, inactivate antitumor factors that control cell growth and avoid the immune system. The investigations carried out also have concluded that the metabolic changes are associated with the activation of oncogenes and the inhibition of tumor suppressors, thus gene changes us closely related to the metabolic rewiring. This specific metabolic alteration of tumor cells allows scientists to think of it as a source of potential therapeutic targets. There are many antitumor drugs against metabolic targets that, used as stand-alone compounds or together with other chemotherapeutics, are analyzed as possible antitumor drugs able to stop tumor growth or even its eradication. The current studies are focused mainly on the bioenergetic pathways and anabolic pathways of the tumor cells, choosing as targets the enzymes, products or intermediates of the glycolysis, the TCA cycle or the pentose phosphate pathway. Unfortunately, tumors are extremely heterogeneous and have a high plasticity due to their different origin, thus the discover of new antitumor drug against metabolic targets is not a simple task. Most of the studies are in early clinical phases and some of them even been interrupted due to the appearance of severe harmful side effects - mainly toxicity-. However, there are many positive results that allow to think that struggle against the tumor metabolism is and will be a promising fight against the cancer