A Faculty of Medicine & Dentistry researcher is taking the fight against ovarian cancer to the molecular level.
YangXin Fu received a three-year, $420,000 grant from the Canadian Cancer Society to continue his work studying how growth and progression of ovarian cancer is controlled, and in particular, the role of nitric oxide.
"Nitric oxide is a gaseous molecule that is produced by cancer cells and cells that surround cancer cells," said Fu. "It triggers signalling pathways that control cell growth and death, as well as the formation of new blood vessels that supply oxygen and nutrients to cancerous tumours."
Fu is looking at soluble guanylyl cyclase (GUCY1B3), an enzyme that is over-expressed in human ovarian cancer tissue and activated by nitric oxide. GUCY1B3 has also been shown to be required for the formation of new vessels. Fu's research is three-pronged, aimed at discovering whether inhibiting the molecule can block the formation of new blood vessels to the tumour, slow the growth of the tumour itself, and possibly make the cancer cells more susceptible to chemotherapy.
"In late stages, basically we treat the patient with surgery to remove the tumour, followed by chemotherapy. While the patient will usually respond to this, after a while the disease will often come back in a chemotherapy-resistant form," he said. "If the traditional chemotherapy doesn't work, that means the tumour has developed a mechanism, or multiple mechanisms, to fight it, so we have to find different strategies."
Fu is investigating whether the nitric oxide signalling pathway can be a therapeutic target for ovarian cancer.
"We are currently doing cell culture work and it's quite promising," he said. "In the cell culture model, if we knock down this gene [GUCY1B3] ... the ovarian cancer cells become more sensitive to chemotherapy drugs. More tumour cells die, and the cancer cells form more slowly."
Ovarian cancer is the fifth leading cause of cancer deaths in women, and the leading cause of gynecologic cancer-related death. Every year, approximately 200,000 women are diagnosed with ovarian cancer worldwide. More than 75 per cent of cases are diagnosed in advanced stages and, despite advances in surgical techniques and chemotherapy, relapses will occur in 85 per cent of patients.
The five-year overall survival for advanced-stage ovarian cancer patients is only 15 to 25 per cent.
An added complication is that patients become less responsive to chemotherapy with each subsequent relapse.