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Making cancer cells lose the battle

Making cancer cells lose the battle

The discovery of an immune-based biomarker will influence treatment options for women with ovarian cancer.

[Dr. Madhuri Koti (left) and lab technologist Nichole Peterson]
Photo by Greg Black

Dr. Madhuri Koti (left) and lab technologist Nichole Peterson

Madhuri Koti, from the Departments of Biomedical and Molecular Sciences and Obstetrics and Gynaecology, has discovered an immune-based biomarker that will help lead to better predictions of the success of chemotherapy in ovarian cancer patients, a discovery that could lead to better treatment options in the fight against ovarian cancer.

"Recent successes in unleashing the immune system to combat cancer are evidence for the fight between a patient’s immune responses and cancer and how we can take advantage of the associated events towards making the cancer cells lose the battle," explains Dr. Koti. "Many of these newer treatments are based on boosting anti-cancer immunity via a single agent or combination therapies that can be overlaid on the standard treatment regimes. Cancer immunotherapies would prove to be most effective when coupled with biomarkers that can predict a patient’s eventual response to the specific therapy, which is key to personalized medicine."

Ovarian cancer leads to approximately 152,000 deaths among women worldwide each year, making it a leading cause of gynaecological cancer-related deaths in women. Dr. Koti conducted the first biomarker study in retrospective cohort of more than 200 ovarian cancer patients. This study utilized a combination of recent cutting-edge and more established detection technologies used for identifying such markers from patient samples. Initial discovery of these markers was made using frozen tumour tissues accrued from tumour banks such as the Ontario Tumour Bank, the Ottawa Health Research Institute, and Gynaecology-Oncology and Pathology services of the CHUM Hospital Notre-Dame, Montreal. The findings from the first study were published in the British Journal of Cancer.

Cancer immuno-therapies would prove to be most effective when coupled with biomarkers that can predict a patient’s eventual response to the specific therapy, which is key to personalized medicine.

The second independent biomarker validation study conducted on tumour samples, accrued from retrospective cohorts of more than 550 ovarian cancer patients, further confirmed the findings and, most importantly, revealed the significant role of this biomarker in bringing cancer-killing immune cells to the tumour environment. The samples used in the study are banked at the Pan-Canadian tumour repository at Terry Fox Research Institute-Ovarian Cancer Canada, partnered with the Canadian Ovarian Experimental Unified Resource.

A major impact of this discovery is that these novel markers, when used at the time of treatment initiation in the specific groups of ovarian cancer patients, will help gynaecologic oncologists make decisions on additional treatment strategies needed for these patients towards increasing the potential for patient survival. Using patient-derived material and animal models, Dr. Koti’s lab at the Queen’s Cancer Research Institute is now exploring genetic factors and mechanisms that underlie the distinct tumour-immune landscapes in ovarian cancer patients.

The study was conducted in collaboration with Drs. Anne-Marie Mes-Masson, Centre de Recherche du Centre Hospitalier de l’Université de Montréal, Montreal, and Jeremy Squire, Faculdade de Medicina de Ribeirão University of Sao Paulo, Brazil. The findings from the second study will be published in The Journal of Pathology: Clinical Research. Funding support for this study was provided by the Cancer Research Society.

[cover of Alumni Review 2016 Issue 3]