Grant Will Fund Breast Cancer Research Aimed at Targeting Protein MED1
Xiaoting Zhang, PhD, a member of the Cincinnati Cancer Center, the UC Cancer Institute and an associate professor in the department of cancer biology at the UC College of Medicine, is receiving a grant supplement from the organization HOPE and the American Cancer Society (ACS) to continue his breast cancer research.
The $100,000 grant will help Zhang’s team further study the function of MED1—a protein found in breast cancer cells that when eliminated is found to stop cancer cell growth—and to determine its significance in the formation of breast tumors and sensitivity to chemotherapy.
"Breast cancer is the most common type of cancer and a leading cause of death among women in the Western hemisphere,” Zhang says. "My initial ACS Research Scholar Grant, awarded in 2012, was based on our unexpected finding that elimination of MED1 in breast cancer cells leads to cellular senescence— essentially a static state of cells.
"Cellular senescence in cancers has been shown to inhibit tumor formation and to enhance the antitumor effect of chemotherapeutic drugs. The objective of this grant is to study how MED1 functions in cellular senescence and to determine its significance in breast tumor formation and chemosensitivity.
"We expect that this study will not only provide more information about the processes controlling cellular senescence but will also provide insights and therapeutic targets for the treatment of human breast cancer in conjunction with lower doses of chemotherapeutic medicine to overcome the major problems cancer patients are facing—high toxicity, resistance and unwanted side effects of the current chemo-therapeutic regiments.”
Zhang says the award of this supplemental grant will allow his research team not only to continue these studies but also to expand and specifically look at the role of MED1-regulated cellular senescence in the spread of human breast cancer, or metastasis. Metastatic breast cancer is the primary cause of death for breast cancer patients; however, not much is known about the molecular pathway involved.
"MED1 is known to express at abnormally high levels in about 40 to 60 percent of human breast cancers, and interestingly, recent studies published in the journal Nature further discovered increased frequency of MED1 mutations in ‘metastasis seeding’ circulating tumor cells in the plasma of breast cancer patients following treatment,” he says.
"We will investigate the functions of MED1-regulated cellular senescence in human breast cancer to help us better understand the molecular mechanisms leading to tumor metastasis and to find more potential therapeutic targets for the treatment of metastatic human breast cancer.”
The team will use cultured human breast cancer cells that have been altered to contain various levels and forms of MED1 and will study the protein’s roles in migration, invasion and metastasis of breast cancer.
"In addition, we will determine how MED1-regulated senescence will affect the metastasis capabilities of neighboring breast cancer cells using both human breast cancer cells and animal models,” Zhang says. "The underlying molecular mechanisms will be further explained through a combination of our established molecular, cellular and histological (anatomical study of the microscopic structure of tissue) approaches.
"We hope that these results will provide more insight to the function of this protein and will lead to more targeted therapies for patients with breast cancer,” he adds. "In fact, part of our research team is currently working on translating our basic research findings by developing a new technology called RNA nanotechnology for therapeutic applications, and we are also teaming closely with clinicians within the UC Cancer Institute’s Breast Cancer Center of Excellence to attain that goal.”