Novel methodologies for the synthesis of unctionalized pyroglutamates
Targeting Tumor Glycolysis for Cancer Therapy:
Tumors are abnormal growth of the tissue formed from unregulated reproduction of cells. the augmented growth results in an increased need in tumor tissue for essential nutrients and energy.
The need for increased energy results in a unique cellular metabolism that results in high consumption of glucose for energy production. Malignant tumors contain aerobic and hypoxic regions, and intratumoral hypoxia increases the risk of cancer advancement, and metastasis.
Tumor hypoxia leads to treatment failure, relapse and, patient mortailty as these cells are generally resistant to standard chemo- and radiation therapy. Under hypoxic conditions, cancer cells upregulate glycolytic enzymes and pursue aggressive glycolysis for energy production. However, using this protocol, each molecule of glucose produces just 2 ATP molecules.
A tumor cell's main energy source is glucose, so the loss in efficacy means the rate of glycolysis is increased, up to 200%. Glycolysis is also the first step in a cell's conversion of glucose to pyruvate for the use in other metabolic reactions, including the citric acid cycle, lactic acid formation, gluconeogenesis, etc.
Inhibition of enzymes and transporters results in the disruption of the glycolysis and consequently the cancer cells will not be able to proliferate and metastasize. Since glycolysis is a common factor in all the cancer cell lines, this strategy should be applicable to the treatment of several cancers.