UToledo Scientist Receives $2.8 Million Grant to Study Breast Cancer

UToledo Scientist Receives $2.8 Million Grant to Study Breast Cancer

Much like we depend on our neighborhood grocery stores, pharmacies and gas stations for all our essentials, tumors rely on their own microenvironment to grow and thrive.

Within those complex microscopic ecosystems are blood vessels, non-cancerous connective tissues, immune cells, proteins and other molecules that cancer cells leverage to flourish and spread.

"There are all these cells bunched together that form the tumor mass, and it has become clear that these non-cancerous cells are key players in disease progression and drug resistance," said Dr. Jianmin Zhang, a professor in the Department of Cell and Cancer Biology.

Understanding these unique tumor microenvironments, Zhang said, is critical for developing new therapies - particularly in cancers that remain challenging to treat, such as triple negative breast cancer.

Accounting for around 15% of all breast cancer cases, triple negative breast cancer is widely considered the most dangerous form of the disease because of its rapid spread and resistance to the targeted therapies that have improved survival rates in other forms of breast cancer.

Zhang is leading a new research project funded by a $2.8 million award from the National Cancer Institute that focuses on the unique role a signaling protein called TAZ plays in the triple-negative breast cancer tumor microenvironment.

TAZ is a key component in what's known as the Hippo singling pathway, which helps to control cell proliferation and cell death in humans and other mammals.

Zhang, who joined UToledo earlier this year from Roswell Park Comprehensive Cancer Center in Buffalo, New York, said TAZ not only promotes cancer growth, but its activation also appears to mobilize myeloid-derived suppressor cells that tamp down the normal immune response - hampering the body's ability to fight the cancer.

And while TAZ is being studied in a number of types of cancer for its role in cell proliferation, Zhang's earlier research suggests it may have an outsized role in triple-negative breast cancer.

"TAZ is highly expressed in triple negative breast cancer, more than in other breast cancers," he said. "High levels of TAZ expression also correlate with worse outcomes in triple negative breast cancer. That's something we don't see in other forms of breast cancer, which gives us the idea that it has a major role in this disease."

In a previous study in laboratory animals, Zhang was able to slow triple negative breast cancer by inhibiting TAZ expression.

With the new grant funding, he and his colleagues will work to more deeply study how TAZ expression impacts the tumor microenvironment, with a particular focus on how it inhibits the immune response.

"We want to understand how these tumor cells are talking with these immune suppressive cells," Zhang said. "If we can understand that, we might be able to block the way TAZ recruits those immunosuppressive cells and let the immune cells in. This could give us new therapeutic targets."

It also could potentially lead to better outcomes for triple negative breast cancer by improving the response rate of immune-based therapy, Zhang said.

"A lot of patients get immune therapy because there is no other specific targeted therapy for triple negative breast cancer," he said. "There are a number of theories about why it often doesn't work. But if we can reduce those immune suppressive cells, we may be able to help improve the effectiveness of immune therapy in triple negative breast cancer. We're not specifically investigating immune therapies, but there could be significant implications."

Public link

Please use the above public link if you want to share this noodl on another website.