Earlier this week I got an email from a boy in China, asking me to send him a compound that was synthesized by one of my lab-mates and was subsequently shown to kill cancer cells. At first I thought the email was spam, but after closer inspection I realized that it wasn't; he wasn't well informed, but had obviously read an article related to our lab's work and wanted the compound to give to his mother. Unfortunately, because this drug is still in pre-clinical phase my lab can't do anything to help cancer patients like this Chinese boy's mother. I felt awful and didn't know what an appropriate response would be to his email.
Anways, this relates to an article that I read at the end of this week entitled "Cancer patients opt for unapproved drug." It was pretty fascinating and made me think. Basically, in January, Bonnet and coworkers [1] at the University of Alberta demonstrated that the small molecule dichloroacetate (DCA) can force cancer cells to undergo apoptosis and decrease tumor growth with limited toxicity. It sounds too good to be true, but the science behind it makes sense. Cancer cells have a unique metabolic profile, as the glucose oxidation that normally takes place in the mitochondria is not functional; thus, the mitochondria is considered "inactive" and the cells rely on cytoplasmic aerobic glycolysis for energy production. As a result of this mitochondrial damage, tumors have increased glucose uptake and metabolism, and this is considered one of the better markers of cancer cells. Studies have shown that several human cancers cell lines have hyperpolarized mitochondria and reduced oxidative metabolism; through inhibition of the mitochondrial enzyme pyruvate dehydrogenase kinase (PDK), DCA is able to reverse these changes to the mitochondria, which in turn allows tumor cells to be killed through apoptosis. Most amazingly, tumor volumes were reduced in of nude rats that drank DCA dissolved in drinking water and no toxicity was observed. As DCA has been used in clinical trials for the treatment of mitochondrial diseases and has a patented structure, big pharma wasn't interested in developing it as a drug.
This is where things start to get a little more interesting. After a little research on DCA, Jim Tassano, the owner of a pest control company in California, teamed up with chemist Joseph Ryan to make DCA. After they came up with a suitable synthesis, he set up two websites: one is devoted to selling this homemade DCA for veterinary use, and the other provides contains excerpts from the Bonnet paper as well as a DCA discussion forum with over 1,000 posted messages. Although the FDA has not approved of the use of DCA in humans, many of the posts on the forum are from cancer patients taking DCA and reporting on its effectiveness, a "clinical trial" of sorts. Researchers are worried that these patients are not only endangering themselves by taking an unapproved drug, but also hindering attempts of completing a real clinical trial. Approximately 95% of cancer drugs in clinical trials don't get approved for human use, usually due to ineffectiveness or undesirable side effects. Sadly many patients don't have time to wait for clinical trials to be completed, and therefore they are willing to subject themselves to the unknown in hopes of beating cancer.
I certainly see both sides of the issue. While the chemist in me cringes at the thought of ingesting any non-pharmaceutical grade chemical (the website that sells DCA claims a purity of more than 99%, with impurities of 0.5% monochloroacetic acid and/or trichloroacetic acid, which doesn't come close to the purity requirements for pharmaceuticals), my compassionate side wants to offer a ray of hope to those suffering.
Anways, this relates to an article that I read at the end of this week entitled "Cancer patients opt for unapproved drug." It was pretty fascinating and made me think. Basically, in January, Bonnet and coworkers [1] at the University of Alberta demonstrated that the small molecule dichloroacetate (DCA) can force cancer cells to undergo apoptosis and decrease tumor growth with limited toxicity. It sounds too good to be true, but the science behind it makes sense. Cancer cells have a unique metabolic profile, as the glucose oxidation that normally takes place in the mitochondria is not functional; thus, the mitochondria is considered "inactive" and the cells rely on cytoplasmic aerobic glycolysis for energy production. As a result of this mitochondrial damage, tumors have increased glucose uptake and metabolism, and this is considered one of the better markers of cancer cells. Studies have shown that several human cancers cell lines have hyperpolarized mitochondria and reduced oxidative metabolism; through inhibition of the mitochondrial enzyme pyruvate dehydrogenase kinase (PDK), DCA is able to reverse these changes to the mitochondria, which in turn allows tumor cells to be killed through apoptosis. Most amazingly, tumor volumes were reduced in of nude rats that drank DCA dissolved in drinking water and no toxicity was observed. As DCA has been used in clinical trials for the treatment of mitochondrial diseases and has a patented structure, big pharma wasn't interested in developing it as a drug.
This is where things start to get a little more interesting. After a little research on DCA, Jim Tassano, the owner of a pest control company in California, teamed up with chemist Joseph Ryan to make DCA. After they came up with a suitable synthesis, he set up two websites: one is devoted to selling this homemade DCA for veterinary use, and the other provides contains excerpts from the Bonnet paper as well as a DCA discussion forum with over 1,000 posted messages. Although the FDA has not approved of the use of DCA in humans, many of the posts on the forum are from cancer patients taking DCA and reporting on its effectiveness, a "clinical trial" of sorts. Researchers are worried that these patients are not only endangering themselves by taking an unapproved drug, but also hindering attempts of completing a real clinical trial. Approximately 95% of cancer drugs in clinical trials don't get approved for human use, usually due to ineffectiveness or undesirable side effects. Sadly many patients don't have time to wait for clinical trials to be completed, and therefore they are willing to subject themselves to the unknown in hopes of beating cancer.
I certainly see both sides of the issue. While the chemist in me cringes at the thought of ingesting any non-pharmaceutical grade chemical (the website that sells DCA claims a purity of more than 99%, with impurities of 0.5% monochloroacetic acid and/or trichloroacetic acid, which doesn't come close to the purity requirements for pharmaceuticals), my compassionate side wants to offer a ray of hope to those suffering.
3 comments:
Are we sure this is aerobic glycolysis and not anaerobic glyclysis. It is my understanding that this mechanism for generating ATP is activated in conditions of insufficient O2
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