Enzyme Inhibition Aids to treat Breast Cancer: New study

Preclinical study led by the Duke Cancer Institute could pave the way to improve susceptibility of breast cancer tumors to the body's immune system.

Enzyme present in macrophages found to regulate the growth and spread of breast cancers. Testing in mice, researchers demonstrated a way to suppress the enzyme's activity which allows T-cells to mount an immune attack on breast cancer cells. The study got published in the journal Nature Communications.

Immunotherapies have transformed cancer care, but their successes have been limited for reasons that are both complex and perplexing. In breast cancer especially, only a small number of patients are even eligible to undergo treatment with immunotherapies, and most see little benefit.

‘New class of drugs which inhibits the enzyme CaMKK2 could be identified soon. They suppress the breast tumor growth by increasing the accumulation of tumor-killing T cells and by reducing the tumor's capability to suppress T cell activity.’
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"We found that inhibition of the activity of this enzyme decreased the ability of macrophages in tumors to suppress an immune attack on cancer cells and indeed encouraged them to start producing chemicals that attract more cancer-killing T cells into the tumor," said Donald McDonnell, Ph.D., chair of Duke's Department of Pharmacology & Cancer Biology. "We can basically uncloak the tumor to the immune system."

McDonnell and colleagues, including lead author and collaborator Luigi Racioppi, M.D., Ph.D., reported that a kinase, or enzyme, called CaMKK2 is highly expressed in macrophages within human breast tumors. They performed a series of exploratory studies that revealed the molecule's potential utility as a therapeutic target for breast cancer. Working with colleagues at the University of North Carolina at Chapel Hill, they developed a new class of drugs that inhibited the growth of human breast tumors grown in mice.

"The use of this molecule suppressed tumor growth not only by increasing the accumulation of tumor-killing T cells, but also by reducing the tumor's capability to suppress T cell activity," McDonnell said. "It's solving two problems, like we couldn't get into the bar, and if we did, we couldn't get a drink. Now we can do both."

McDonnell said additional studies are ongoing, with the goal of acquiring data to launch a clinical trial in breast cancer patients within the next 18 months.

Source-Eurekalert