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Case Studies and Reviews
First Preclinical Study
Dr. Ko's first preclinical study was more successful than anyone could have imagined. This mouse model seeded 34 mice with hepatocellular carcinoma with 19 mice treated with 3BP and 15 untreated mice serving as controls. All 19 treated mice were completely cured and lived out a normal lifespan, while all 15 controls had to be euthanized.
Second Preclinical Study
Though the second preclinical study does not appear to be as dramatic or spectacular as the first, that understanding is far from true. In many ways, Dr. Ko feels that the significance of the second study was critical for her to validate the safety and potential toxicology of KAT ultimately for human use.
Third Preclinical Study
This preclinical study was in partnership with the University of Maryland in 2018 and tested KAT’s effectiveness in conjunction with Radiation Therapy (RT). These results have been particularly exciting, as it was designed to explore the effect of 3BP on tumor growth in non-small cell lung cancer.
Fourth Preclinical Study
3-Bromopyruvate Inhibits Pancreatic Tumor Growth by Stalling Glycolysis
and Dismantling Mitochondria in a Syngeneic Mouse Model
American Journal of Cancer Research - Volume 12, Number 11:4879-5350; 2022
This study was completed as a collaborative project with the Radiation Oncology Research Department at the University of Maryland School of Medicine. For the last five years, the University of Maryland has been an important partner with Dr. Ko to provide independent confirmation of her work validating the efficacy of KAT 3-BP. A University of Maryland future study is currently in the planning stages, which will seek to determine the impact of a longer KAT 3-BP protocol on cancer stem cells and the metastatic spread of pancreatic cancer.
Highlights and key points from the Study Abstract
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Pancreatic cancer (PC) is the fourth-most-deadly cancer in the United States with a 5-year survival rate of only 8%. The majority of patients with locally advanced pancreatic cancer undergo chemotherapy and/or radiation therapy (RT).
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3-Bromopyruvate (3-BP) is a promising anticancer drug against pancreatic cancer. It exerts potent anticancer effects by inhibiting hexokinase II enzyme (HK2) of the glycolytic pathway in cancer cells while not affecting the normal cells.
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KAT 3-BP killed 95% of Panc-2 cells... and severely inhibited ATP production by disrupting the interaction between HK2 and mitochondrial Voltage Dependent Anion Channel-1 (VDAC1) protein.
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Electron microscopy data revealed that 3-BP severely damaged the mitochondrial membrane in cancer cells.
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Immunohistochemistry data showed complete inhibition of hexokinase II (HK2) and TGFβ, in animals treated with 3-BP drug.
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We also observed enhanced expression of active caspase-3 in tumor tissues exhibiting apoptotic death.
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Importantly, we also observed inhibition in lactic acid production responsible for tumor aggression.
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These results provide new evidence that 3-BP severely inhibits glucose metabolism in cancer cells by blocking hexokinase II, and disrupting mitochondria by suppressing BCL2L1 in pancreatic cancer.
