3-BROMOPYRUVIC ACID As a Potent Anticancer Agent Delivered Intraarterially
Liver cancer is one of the most common fatal cancers in the world and may reach epidemic levels in the future due to increased viral hepatitis. Current treatment options are rarely successful indicating a real need for alternative therapies. We have developed a new approach based on delivering the chemical agent 3-bromopyruvate intraarterially directly into liver tumors that are fed primarily by arteries. Significantly, 3-bromopyruvate is a strong alkylating agent that inhibits both sources of energy for cell survival, i.e., glycolysis and mitochondrial oxidative phosphorylation. In animal studies using a rabbit model for liver cancer, we have shown that 3-bromopyruvate, in a single bolus intraarterial injection, kills up to 90% of the tumor cells within tumors growing within the liver. The surrounding liver tissue remains viable, other organs show no apparent damage upon pathological examination, and the animals remain healthy. Additionally, we have shown that 3-bromopyruvate when injected systemically (intravenously) to such animals suppresses the growth of metastatic lung tumors that appear to arise from metastasis of the liver tumors. Again, there is no apparent damage to other organs and the animals appear healthy Description (Set) Proposed Use (Set) This invention offers a new potent anticancer agent (3-bromopyruvate) for hepatocellular carcinomas, and at the same time offers a direct approach for delivering an anticancer agent to liver tumors. The agent 3-bromopyruvate may have widespread application as a general anticancer agent for many other tumors, e.g., lung tumors, and the direct delivery method is expected to be applicable to tumors growing in tissues other than the liver. Provided its concentrations are maintained below toxicity levels, 3-bromopyruvate may have widespread application also in suppressing or defeating many metatstatic tumors, and in suppressing certain forms of leukemia. Finally, structural analogs of 3-bromopyruvate, or new chemical derivatives of this agent may also prove to be effective anticancer agents both for primary and metastatic tumors.
Ko, Young H.
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