US Army funds “innovative concept” to boost effect of chemotherapy

Kingston, ON February 28, 2003 A Queen’s University research team that recently discovered a way to make breast cancer cells more responsive to chemotherapy is now investigating whether a similar procedure can effectively treat prostate cancer the second leading cause of cancer deaths for men in North America.

Dr Charles Graham, of the Dept of Anatomy and Cell Biology, will lead a Queen’s group of investigators in the study, which has been awarded a US$300,000 Idea Development Award from the US Army’s Prostate Cancer Research Program.

Working with Dr Graham on the Queen’s prostate cancer research team is urologist Dr Robert Siemens. Other collaborators in the research that led to this grant include Drs Michael Adams (Pharmacology and Toxicology) and Jeremy Heaton (Urology).

The study is based on earlier findings that tumour cells exposed to very low levels of oxygen become resistant to the killing effects of anti-cancer drugs. Reduced oxygen levels contribute to the drug resistance by blocking the production of nitric oxide (NO) in the tumour cells.

"This was an exciting finding because it opened the possibility of using drugs such as nitroglycerine, which deliver NO or mimic its effects, to increase the sensitivity of cancers to conventional anti-cancer drugs," says Dr Graham. "Most patients who die of prostate cancer do so because the tumour spreads and fails to respond to therapy."

Additional benefits of nitroglycerine a drug that has been used to treat chest pain for more than 100 years are that it is relatively inexpensive and that it has no significant side effects.

In assessing the grant application from the Queen’s team one of only 18 percent that were successful the US Department of Defense review panel placed the proposal in the 98th percentile. Praising Dr Graham’s "innovative concept", the summary stated that "the review panel was highly supportive of this outstanding proposal."

The researchers will administer nitroglycerine, as well as other ‘NO mimetic’ drugs, to human and rodent prostate cancer cells, to test whether this is a feasible approach for increasing the sensitivity of prostate cancers to anti-cancer drugs. They also hope to develop a better understanding of how prostate cancer cells become resistant to chemotherapy.

"While this research may result in new approaches to the treatment of patients with prostate cancer, it also has the potential of leading to novel ways of enhancing the efficacy of chemotherapy against other cancers, such as breast cancer," says Dr Graham.