Glycolysis Inhibitors
Upregulation of glycolysis with increase in glucose consumption for metabolic pathways to generate ATP is the universal property of all the cancers and tumors. This phenomenon is known as Warburg™s effect and is known to be an important process in metabolic alterations during malignancy. Many biochemical and molecular studies have come up with different explanation of this altered mechanism including mitochondrial defects and malfunction, adaptation to hypoxic tumor microenvironment, oncogenic signaling and abnormal expression of metabolic enzymes. The most important is the dependence of cancer cell metabolism on glycolytic pathway for generation of ATP. This makes the biochemical basis of therapeutic design and strategies to kill cancer cells by targeting pharmacological inhibition of glycolysis. Many small molecules have emerged exhibiting promising anti-cancer activity as single agent in combination with other therapeutic modalities. These glycolytic inhibitors are especially effective against cancer cells with defective mitochondria or are under hypoxic conditions, since hypoxia is present in most tumor micro environment. The development of novel glycolytic inhibitors as anticancer agents is bound to have broad therapeutic applications. The glycolytic inhibitors can also be targeted towards malignancies associated with cellular resistance to conventional drugs and radiation therapy.
