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Breast cancer is the second most common cancer for women in the United States, and its incidence has incrementally increased over the past three decades. Minority populations are more significantly affected: breast cancer is the leading cause of cancer death among Hispanic women, and Black women have a higher rate of death from breast cancer than white women.

Several researchers from VCU Massey Cancer Center have received National Institutes of Health (NIH) grants to study key aspects of the disease: the role of a DNA repair pathway in the development of breast cancer tumors, and a new combination of drugs to effectively treat breast cancer while mitigating damage to the heart caused by a common chemotherapy medication.

Hua Zhao, Ph.D., Cancer Prevention and Control research member at Massey and professor in the Department of Family Medicine and Population Health at the VCU School of Medicine, received a U01 grant of $2.5 million over 5 years from the National Cancer Institute (NCI) to further study the role of a DNA repair pathway, homologous recombination repair (HRR), in the development of breast cancer.

“In order to better predict breast cancer risk and ultimately reduce the disease burden on our population, it is vital that we understand the scientific underpinnings of the disease, including the role of these repair pathways,” said Zhao. “This grant will allow us to test our hypothesis that suboptimal HRR capacity leads to an increased accumulation of DNA damage and an elevated risk of breast cancer.”

Zhao and his team have developed a non-invasive tool to measure HRR capacity in peripheral blood lymphocytes (PBLs), white blood cells that circulate throughout the body and play a role in the tumor-related immune response. The team’s preliminary studies have indicated that HRR capacity was significantly lower in breast cancer cases than in the control group. Now, using large-scale genetic and genomic datasets including the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO), the group seeks to validate HRR capacity in PBLs as a breast cancer risk factor, and understand the genetic determinants of HRR in PBLs.

Co-principal investigators Rakesh Kukreja, Ph.D., Developmental Therapeutics research member at Massey and Eric Lipman Professor and the former scientific director of VCU Pauley Heart Center, and Anindita Das, Ph.D., associate professor in the Division of Cardiology at the VCU School of Medicine, have been awarded a 4-year, $2.2 million R01 grant to study a novel combination treatment for breast cancer to reduce the risk of heart failure, a common side effect of doxorubicin (DOX) chemotherapy.  

DOX alone or in combination with a kinase inhibitor is highly effective in treating breast cancer, but survivors treated with DOX are at risk of early cardiovascular morbidity and mortality. Currently there is no effective therapy available to reduce or eliminate this risk. Kukreja, Das and their team will study the therapeutic effect of the combination of DOX or DOX with a kinase inhibitor, sildenafil (commercially known as Viagra) — the widely-known impotence drug previously found to improve the effectiveness of cancer treatment while protecting the heart from damage — and the anti-rejection drug rapamycin to reduce cardiac side effects and improve the efficacy of breast cancer treatment in breast cancer-bearing mice.

“Because sildenafil and rapamycin are clinically approved drugs, the results of these studies could help in developing a successful combination therapy for treatment of thousands of breast cancer patients experiencing the lethal and debilitating cardiotoxic effects of chemotherapy treatment worldwide,” said Kukreja and Das.

Written by: Annie Harris