Gelsolin: Kill Chemo-Resistant Ovarian Cancer Cells By Killing Their Protector

Ovarian cancer is the most deadly gynecological kind, it claims the lives of more than 50% of women who are diagnosed Ovarian cancer is often diagnosed late and develops a resistance to chemotherapy but new insight into why may lead to better diagnosis and treatment.

Ovarian cancer is the most deadly gynecological kind, it claims the lives of more than 50% of women who are diagnosed

Ovarian cancer is often diagnosed late and develops a resistance to chemotherapy but new insight into why may lead to better diagnosis and treatment.

"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.

"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.

Citation: Mohammad R. Abedini, Pei-Wen Wang, Yu-Fang Huang, Mingju Cao, Cheng-Yang Chou, Dar-Bin Shieh, and Benjamin K. Tsang, 'Cell fate regulation by gelsolin in human gynecologic cancers', PNAS September 22, 2014, DOI: 10.1073/pnas.1401166111. Source: Ottawa Hospital Research Institute
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