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Contemporary Perspectives on the Warburg Effect Inhibition in Cancer Therapy

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johan
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https://journals.sagepub.com/doi/full/10.1177/10732748211041243

excerpt on 3BP

The 3-bromopyruvate is an excellent example of the difficulties associated with the search for effective drugs. 3BP showed great effectiveness in studies using cell lines and tumor xenograft animal models,70 raising hopes for developing a fast, powerful agent for cancer treatment. The 3BP has not yet undergone formal clinical trials but it was used in two single-case trials. In 2012, Ko and co-workers reported on the usage of 3BP in the treatment of a 16-year-old patient diagnosed with fibrolamellar hepatocellular carcinoma in the terminal phase.71 The authors suggested that 3BP treatment did not cause significant toxicity to the patient and let him survive for two more years with a higher quality of life than expected. Finally, the patient died not from cancer, but due to liver function overload, unable to eliminate the dead cancer cell debris formed after 3BP treatment.71 In another report, in 2014, El Sayed and co-workers used 3BP to treat a 28-year-old patient diagnosed with stage IV metastatic melanoma.72 Intravenous infusion of 3BP caused a burning venous sensation but there were no severe toxic effects. Unfortunately, in this case, the patient died a few months after starting the 3BP treatment due to complications related to the advanced stage of the tumor.72 It is important to mention that 3BP was also used as part of alternative therapy. In Germany, in 2016, three patients undergoing alternative cancer treatment died shortly after the infusion of 3BP, and non-medical practitioners had been charged with involuntary manslaughter.73

At present, it is known that free, unformulated 3BP could not be used for patient treatment. Apart from discounting side effects, such as a burning venous sensation accompanying the intravenous 3BP infusion, we have to be aware of many other obstacles, for example, the inactivation of 3BP by serum proteins and high GSH level. Moreover, despite 3BP’s effectiveness in killing glioblastoma cells, its utility in brain cancer treatment is hindered due to its inability to cross the blood–brain barrier. However, some of these obstacles can be overcome. Formulating 3BP with liposomal carriers or suitable nanoparticle carriers could potentially enable 3BP to cross the blood–brain barrier and prevent its inactivation in blood.39 Mixing 3BP with citric acid might result in better persistence of the compound in tumor tissue, and combining 3BP with a GHS depleting agent might overcome the resistance in GHS-rich tumors.39

 


   
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Jcancom
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Joined: 6 years ago
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johan, thank you for posting this article. I am sure that you knew that I would be interested! I think that with 3-BP about ready to enter the clinic we have firmly entered into the Metabolic era of cancer treatment. One strong topline treatment such as 3-BP could be base upon which an entire treatment strategy could emerge. We have seen that patients need at least one lead therapy and then everything can combine from there. 3-BP now has a great many combinations that will amplify its effects. Very Exciting!  


   
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