Grant: Travel Awards - Institute Community Support

Breast Cancer gene 2 or BRCA2, is a gene found in all humans. BRCA2 plays a very important role in most cell types. Loss of BRCA2 function because of mutation, mainly causes breast cancer. Doxorubicin, a medication commonly used for chemotherapy to treat breast cancer, is also on the World Health Organization's List of Essential Medicines. In addition, it is the most important medication needed in a basic health system. There are several common side effects of doxorubicin that include hair loss, vomiting, skin reactions etc.; however, the most dangerous side effect of doxorubicin is heart failure. Despite great medical advances, therapies are urgently needed to improve the heart function after doxorubicin treatment. Endothelial cells, which line the innermost layer of blood vessels, play important roles in maintaining blood vessel function. Endothelial malfunction can cause heart failure. Therefore, understanding the mechanisms underlying endothelial malfunction may provide novel therapeutic approaches to treat doxorubicin-associated heart failure and related malfunctions. Our aim is to understand if loss of endothelial BRCA2 results in increased endothelial cell death and endothelial malfunction that might lead to heart failure after doxorubicin treatment in cancer patients. Our result shows that BRCA2-deficient endothelial cells are more sensitive to doxorubicin treatment. Doxorubicin treatment caused increased death and malfunction in BRCA2-deficient endothelial cells. Our study will show an entirely new role of BRCA2 as a regulator of endothelium function, and provide important clues regarding an increased probability of BRCA2 mutation carriers to doxorubicin-associated endothelial malfunction and heart failure.