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Metabolic alterations in cancer cells and their implications in the therapy of acute leukemias
Harárová, Alžbeta ; Starková, Júlia (advisor) ; Mrvová, Silvia (referee)
Cancer metabolism differs from that of the healthy cells in several aspects. Aerobic glycolysis (e.g. converting pyruvate to lactate under normoxic conditions) was the first described metabolic alteration of cancer cells. Metabolic alterations have since been described in the tricarboxylic acid cycle, oxidative phosphorylation, in the metabolism of amino acids (especially glutamine, asparagine and serine) and also in the metabolism of fatty acids and cholesterol. The common feature of these changes is the tendency to prefer anabolic pathways, thus enabling fast proliferation of cancer cells. The study of cancer metabolism is particularly important in the case of cancer cells that show resistance to treatment, as their aberrant metabolism is not only a potential diagnostic marker but also a potential therapeutic target. The majority of metabolic alterations have been described for the first time in solid tumors, whereas only recently has the metabolism of acute leukamias gained more attention. Asparaginase is an example of a chemotherapeutic agent that targets a metabolic alteration of leukemic cells. Distinct metabolic profile is also associated with the glucocorticoid resistance. Detailled study of the metabolic alterations of leukemic cells has elucitated the mechanisms of the asparaginase and...
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Targeted cancer therapy based on altered metabolism of amino acids
Šafrhansová, Lucie ; Starková, Júlia (advisor) ; Zelenka, Jaroslav (referee)
The effects of targeted therapies in the treatment of cancer have been extensively researched and tested in many clinical trials. In contrast to conventional chemotherapy treatment, targeted therapy should act specifically on cancer cells with limited toxicity and lower risk of side effects. One type of targeted therapy exploits the Achilles heel of cancer - the specificity of tumour metabolism. With knowledge of the metabolic differences between tumor and normal cells, we can set up conditions that normal cells easily bridge, while tumor cells die as a result. This can be achieved by removing certain amino acids from the extracellular environment on which cancer cells depend. A well-known enzyme that has been used therapeutically for many years is asparaginase. However, asparaginase therapy is only successful in some cancers, so further development is needed, as well as the search for enzymes with similar effects. Over the years, four other enzymes that could become an integral part of the treatment of cancer patients in the future have been discovered - arginine deiminase, arginase, methioninase and cyst(e)inase. Past and current studies have investigated their effects on cancer cells in vitro and in vivo. Successful elimination of cancer cells often comes with limitations as immunogenicity and...
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Metabolic alterations in cancer cells and their implications in the therapy of acute leukemias
Harárová, Alžbeta ; Starková, Júlia (advisor) ; Mrvová, Silvia (referee)
Cancer metabolism differs from that of the healthy cells in several aspects. Aerobic glycolysis (e.g. converting pyruvate to lactate under normoxic conditions) was the first described metabolic alteration of cancer cells. Metabolic alterations have since been described in the tricarboxylic acid cycle, oxidative phosphorylation, in the metabolism of amino acids (especially glutamine, asparagine and serine) and also in the metabolism of fatty acids and cholesterol. The common feature of these changes is the tendency to prefer anabolic pathways, thus enabling fast proliferation of cancer cells. The study of cancer metabolism is particularly important in the case of cancer cells that show resistance to treatment, as their aberrant metabolism is not only a potential diagnostic marker but also a potential therapeutic target. The majority of metabolic alterations have been described for the first time in solid tumors, whereas only recently has the metabolism of acute leukamias gained more attention. Asparaginase is an example of a chemotherapeutic agent that targets a metabolic alteration of leukemic cells. Distinct metabolic profile is also associated with the glucocorticoid resistance. Detailled study of the metabolic alterations of leukemic cells has elucitated the mechanisms of the asparaginase and...
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