Olga Stenina Adognravi, PhD

Cleveland Clinic Lerner Research Institute

Breast Cancer

Pilot Grant

Regulation of diabetes-associated breast cancer growth by engineered bacteria normalizing gut microbiome

Breast cancer (BC) growth is accelerated by diabetes and is associated with a pro-inflammatory alterations in gut bacteria. Diabetes also causes pro-inflammatory alteration of gut bacteria, and this may be a major pathway of its effect on BC growth.

In this application, we propose to restore the production of thrombospondin-1, a secreted protein that may maintain healthy gut bacteria and is suppressed in diabetes, by engineering and administering bacteria producing thrombospondin-1 and its fragments and peptides. Populating the gut of mice with experimental diabetes and BC with these bacteria will restore a healthy gut microbiome and inhibit BC growth.

This approach may be used in the future to aid in prevention and treatment of BC in diabetic patients, who are at higher risk for breast cancer and worse outcomes. Although diabetes incidence reaches almost 20% in BC patients and greatly accelerates and aggravates cancer, diabetic patients are treated using the same approaches as in non-diabetic patients, despite lower efficiency of treatments and worse prognosis in diabetic patients. The diabetic patients are often excluded from clinical trials of anti-cancer drugs and therapies. Our work will develop novel breakthrough approach to BC treatment in diabetic patients that can be used in prevention and treatment of BC and may be useful in controlling other complications of diabetes. This approach will complement existing strategies and will offer a more holistic strategy to aid in host defense against cancer, because single pathway therapies designed to target specific pathways (angiogenesis, cancer cell division, etc.) fail.

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