Bromopyruvic acid

Bromopyruvic acid, or bromopyruvate, is a synthetic brominated derivative of pyruvic acid. It is being studied as a potential treatment for certain types of cancer. Initial studies in laboratory animals by Young Hee Ko at Johns Hopkins University showed that bromopyruvic acid is effective at eliminating aggressive liver tumors.^[1]

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According to the Warburg hypothesis, unlike normal tissues that derive most of their energy in the form of adenosine triphosphate (ATP) by metabolizing glucose in the mitochondria, aggressive cancers obtain much of their ATP by metabolizing glucose directly to lactic acid.^[2] The mechanism of action of bromopyruvic acid involves interruption of this latter process by the inhibition of the enzyme hexokinase II, due to the fact that the bromopyruvic acid is similar in chemical structure to lactic acid.^[1]

Further study demonstated that when 19 rats with advanced cancers (generated by seeding with hepatocellular carcinoma cells) were treated with bromopyruvic acid, the cancers were eradicated without apparent toxicity or recurrence in all treated animals.^[3] Another study reported that intraarterial delivery of bromopyruvic acid directly to the site of a tumor, followed by systemic delivery only when necessary, represents a new strategy for stopping the growth of liver and other cancers, while minimizing toxic side effects.^[4]

While pre-clinical studies have been promising, human clinical trials to study the effectiveness of bromopyruvic acid have not yet begun. One obstacle to further development of bromopyruvic acid as a pharmaceutical treatment for cancer is that since bromopyruvic acid is not a novel chemical compound, it is not patentable.^[5] Without the exclusivity allowed by patent protection, there is little prospect for recovery of the high financial investment needed for conducting the clinical trials required by worldwide regulatory agencies for approval of pharmaceutical drugs.

References

Vali M, Liapi E, Kowalski J, Hong K, Khwaja A, Torbenson MS, Georgiades C, Geschwind JF. Intraarterial therapy with a new potent inhibitor of tumor metabolism (3-bromopyruvate): identification of therapeutic dose and method of injection in an animal model of liver cancer. J Vasc Interv Radiol. 2007 Jan;18(1 Pt 1):95-101. PMID: 17296709 [[1]]