Canadian researchers probe nitroglycerin’s effectiveness in treating prostate cancer
KINGSTON, Ontario—For more than 150 years, nitroglycerin has been used for various purposes, and is mostly known for commonly being prescribed to treat heart conditions—but new research out of Canada's Queens University indicates that nitroglycerin may also be effective in treating prostate cancer.
According to the researchers, if their Phase II clinical trial efforts prove successful, their findings could have a game-changing impact on the way we treat prostate cancer and potentially other difficult-to-treat types of cancer.
Prostate cancer, which is the second-most frequently diagnosed cancer and the sixth-leading cause of cancer death in men worldwide, is in most cases slow-growing and symptom-free, and often metastasizes from the prostate to other parts of the body, particularly the bones and lymph nodes. Depending on a patient's age and overall health, stage of disease and genetic factors, treatment options are radiation therapy and/or a
In 2009, Queens University scientists Drs. Robert Siemens and Charles Graham published the results of the first-ever clinical trial in which low doses of nitroglycerin were used to treat prostate cancer. The study showed that nitric oxide-mimicking agents such as nitroglycerin were effective in overcoming cancer cells' resistance to immune attack. This initial study also showed that the use of nitroglycerin significantly slowed the progression of the disease in men with recurrence after their original treatment.
Now, Siemens and Graham, who work for the university's Department of Biomedical and Molecular Sciences, hope to build on their earlier work by conducting a Phase II trial that will specifically study the effectiveness of nitroglycerin on prostate cancer.
Nitroglycerin is converted to nitric oxide in the body by mitochondrial aldehyde dehydrogenase, and nitric oxide is a natural vasodilator.
"In many ways, nitric oxide behaves like oxygen," explains Graham. "We have been interested in studying hypoxia and how low levels of oxygen contributes to the malignant progression of tumor cells, metastasis and therapy resistance. If you put oxygen back into this equation, you can stop this malignant behavior. We came up with a new concept in which nitric oxide interferes with the way that tumor cells interfere with cell signaling."
The researchers are currently recruiting 60 patients with prostate cancer to participate in a randomized, double-blind, placebo-controlled trial. Graham says prostate cancer is a good choice for studying the effects of nitroglycerin because the only indication the disease is recurring is a patient's level of prostate-specific antigen (PSA), a protein produced by cells of the prostate gland.
"Other than that, there are no other overt signs of disease," says Graham. "For that reason, these patients don't get any other kind of therapy. This makes them an ideal group to look at. By comparison, in breast cancer, for example, patients are usually treated aggressively."
In the study, which will be conducted at the Centre for Applied Urological Research at Queen's University, some patients will get a placebo patch; some will get a low-dose nitroglycerin patch; and another group will get a higher-dose nitroglycerin patch. Fourteen patents have been issued to Queen's research discoveries in the use of nitroglycerin and similar compounds for the treatment of cancer. PARTEQ Innovations, the technology transfer office of Queen's, has already licensed some of this intellectual property to Nometics Inc., a spinoff pharmaceutical company that is developing products and therapies based on this and related research.
"For the next phase of the clinical trials, we hope to have a commercially made patch with the right dose," says Graham.
The findings could have applications for other conditions, including pregnancy complications and inflammatory diseases. Graham adds that nitroglycerin also has a high safety profile, "and the main side effect is a headache."
Graham concedes that using a century-old, inexpensive drug to treat prostate cancer and other diseases is "not a blockbuster enterprise," but he notes, "there are so many men in this situation that can benefit from this treatment. If we can come up with something that is an alternative to aggressive therapies, this will give them better quality of life."
"The problem with Big Pharma is they are often not interested in finding new uses for old drugs because their business model is based on creating new blockbuster drugs," he says. "But even though nitroglycerin is inexpensive, we think that by producing a lot of these patches, there is opportunity for profit."
The study is being funded by Ontario's Academic Health Science Centre Alternative Funding Plan Innovation Fund, with additional support from Nometics. The ongoing preclinical research that led to this study is funded by the Canadian Institutes of Health Research.