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Metabolism/Glycosylation Inhibitors
"Targeting Cancer’s Sweet Tooth
Science has recognized that many types of cancer cells have a unique metabolism, distinct from that of normal cells. Cancer cells’ dependence on glycolysis (a specific way of converting glucose into energy) to proliferate and metastasize has been described as the “Sweet tooth of cancer” and is a classic example of how the metabolisms of cancer cells and normal cells differ. Glycolysis is a glucose-intensive means of producing energy that is used by normal cells only if oxygen levels are low. However, many types of tumor cells are essentially addicted to glycolysis even in the presence of abundant oxygen. This is known as the “Warburg Effect” after its discoverer, Dr. Otto Warburg, and such tumors are said to be highly “glycolytic.”
This phenomenon of tumors relying preferentially on glycolysis and the resulting dramatic increase of glucose uptake to fulfill their metabolic demands has already been utilized very effectively in cancer diagnostics. It is the Warburg Effect that enables imaging of actively growing tumors by positron emission tomography (“PET scans”). This diagnostic test uses a fluorine-18 radiolabeled glucose decoy called F18DG that accumulates disproportionately in tumors, using the same process that increases glucose uptake and retention in cancer cells.
The success of PET scanning points to the potential therapeutic benefit of the tumor-specific inhibition of glycolysis that would block energy (adenosine triphosphate (“ATP”)) production and could potentially “starve tumor cells to death” and/or make them sensitive to other existing therapies, including radiotherapy. Unsuccessful attempts to realize this therapeutic potential have been made in the past, using a glucose decoy known as “2-deoxy-D-glucose” (2-DG). Those attempts to target the metabolism of tumor cells have failed, we believe, because of 2-DG’s lack of drug-like properties that include rapid metabolism, short half-life and limited tissue-organ distribution. Essentially, not enough 2-DG could be delivered to its intended target.
We have designed and are studying a novel and patented prodrug of 2-DG (WP1122). We believe WP1122 has the potential for developing into a technology platform for enabling increased cellular uptake, increased drug half-life and, importantly, enabling greater uptake and retention in organs where the most resistant and glycolytic tumors are localized, including the brain and pancreas..."
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