A Way to Kill Chemo-Resistant Ovarian Cancer Cells: Cut Down Their Protector

A recent study provides new insight into why ovarian cancer is often resistant to chemotherapy, as well as a potential way to improve its diagnosis and treatment.

Protein Data Base 3-D rendering of the Gelsolin protein. (Photo: Wikipedia)

Protein Data Base 3-D rendering of the gelsolin protein. (Photo: Wikipedia)

Ovarian cancer is the most lethal gynecological cancer, claiming the lives of more than 60% of women who are diagnosed with the disease. A study involving Ottawa and Taiwan researchers, published in the influential Proceedings of the National Academy of Sciences (PNAS), provides new insight into why ovarian cancer is often resistant to chemotherapy, as well as a potential way to improve its diagnosis and treatment.

It is estimated that 2,700 Canadian women will be diagnosed with ovarian cancer in 2014 and that 1,750 Canadian women will die from the disease, according to Ovarian Cancer Canada. This cancer is often diagnosed late and develops a resistance to chemotherapy.

tsang_ben

Dr. Ben Tsang

“What we’ve discovered will help clinicians to better treat women with ovarian cancer,” says Dr. Ben Tsang, senior scientist at the Ottawa Hospital Research Institute and professor at the University of Ottawa. “The key is understanding the role of a protein called “gelsolin.” With our colleagues from National Cheng Kung University in Taiwan, we found that an increased level of this protein is associated with aggressive forms of ovarian cancer that are more likely to be resistant to chemotherapy and lead to death.”

The researchers showed how gelsolin works at the molecular level to protect cancer cells against a widely used chemotherapy drug called “cisplatin.”

The findings are important because they will help clinicians to determine the most effective treatment plan based on the level of gelsolin. Work still needs to be done to determine exactly how much gelsolin indicates a cancer that is chemo-resistant and would require different treatment options.

In addition, this same protein that makes ovarian cancer cells resistant to chemotherapy can be used to overcome this treatment obstacle. By cutting gelsolin down to a specific fragment and putting it into chemo-resistant cancer cells, the international team discovered they could make these cells susceptible to the cancer-killing effects of cisplatin.

Shieh

Dr. Dar-Bin Shieh

“We believe this discovery is a promising avenue for developing a new therapy to reduce chemo-resistance in women with this deadly disease,” said Dr. Dar-Bin Shieh, collaborative partner from National Cheng Kung University of Taiwan. Shieh is currently leading the International Institute of Macromolecular Analysis and Nanomedicine Innovation (IMANI), which is focused on translating molecular discoveries to the clinic.

Based on 2009 estimates, approximately one in 72 Canadian women will develop ovarian cancer in her lifetime and one in 93 will die from it.

This study was supported by the Canadian Institutes of Health Research and the National Science Council of Taiwan.

Ottawa Hospital Research Institute
The Ottawa Hospital Research Institute is the research arm of The Ottawa Hospital and is an affiliated institute of the University of Ottawa, closely associated with its faculties of Medicine and Health Sciences. The Ottawa Hospital Research Institute includes more than 1,700 scientists, clinical investigators, graduate students, postdoctoral fellows and staff conducting research to improve the understanding, prevention, diagnosis and treatment of human disease. Research at Ottawa Hospital Research Institute is supported by The Ottawa Hospital Foundation.

University of Ottawa: A crossroads of cultures and ideas
The University of Ottawa is home to almost 50,000 students, faculty and staff, who live, work and study in both French and English. The campus is a crossroads of cultures and disciplines, where bold minds come together to inspire game-changing ideas. The University of Ottawa is one of Canada’s top 10 research universities — our professors and researchers explore new approaches to today’s challenges. One of a handful of Canadian universities ranked among the top 200 in the world, we attract exceptional thinkers and welcome diverse perspectives from across the globe.

National Cheng Kung University
National Cheng Kung University (NCKU) is a research-led comprehensive university in Tainan City, Taiwan. Since its establishment in 1931, NCKU has nurtured countless social elites and leaders under the trailblazing efforts of its former faculties and staffs. NCKU is one of the most prestigious universities in Taiwan, with a high reputation in science, engineering, medicine, management, planning and design. The university is a role model for the transformation of Taiwan’s higher-educational institutes, and is also an important pillar of the country’s economic and industrial structure.

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