Gene Involved in Breast Cancer Growth May Speed Precision Medicine

A team from UT Southwestern (UTSW) has found that a significant number of breast cancer patients have higher levels of the ZMYND8 gene, making it a potential target for immunotherapies and precision medicine treatments, according to a study published in Cancer Research.

In the US, about one in eight women will develop breast cancer at some point in their lifetime, researchers noted. Globally, breast cancer is the most common type of cancer and the second leading cause of cancer death among women.

Researchers found that ZMYND8 regulates the stability of an organism’s DNA, or genome. When a cell’s DNA is damaged, the genome becomes unstable and signals the body to destroy the cell through use of the immune system. Specialized cells called lymphocytes then infiltrate DNA-damaged cells to stop them from propagating.

While genome instability is a hallmark of cancer, some cancer cells develop immunity from this response, but researchers don’t completely understand how.  

UTSW researchers found that high levels of ZMYND8 in breast cancer cells suppress antitumor immunity by inhibiting DNA damage and preventing lymphocytes from finding the cancer cells.

“The gene ZMYND8 is increased in breast cancer conditions, and higher levels of the gene correlate with poor survival of breast cancer patients,” said Yingfei Wang, PhD, assistant professor of pathology and neurology and corresponding author of the study. “It could be a promising target for antitumor immunotherapy.”

The team set out to find out what would happen to breast cancer cells if they removed or knocked out the gene for ZMYND8. When they did so in breast cancer cells in mouse models, researchers discovered that lymphocytes were able to invade the tumors and prevent growth.

Researchers will need to conduct further studies to determine whether reducing ZMYND8 in humans will have the same effect as it did in mouse models. But the team did find that this gene is upregulated in approximately ten percent of breast cancer patients, making ZMYND8 a viable target for precision medicine treatments that warrants further investigation.

“We are very interested in identifying small molecule inhibitors of ZMYND8,” said Weibo Luo, PhD, assistant professor of pathology and pharmacology and another corresponding author of the study.

Finding such inhibitors would help researchers develop a new treatment for breast cancer patients that could be used alone or in combination with other treatments like immunotherapy. The team noted that the research is still in its early stages, and that there is still a lot to understand about this gene.

“We don’t know if this gene is critical for maintaining genome stability under physiological conditions,” said Wang. “We need to be really cautious moving forward.”

Identifying ways to target ZMYND8 in breast cancer cells will be critical to avoid interfering with other organ systems. The team is currently examining the physiological role of ZMYND8 through mouse models.

“ZMYND8 can control tumor progression and spread, or metastasis. The protein is very important, at least in breast cancer, and if we can find inhibitors, we can combine them with other therapies for breast cancer treatment,” said Luo, who is a Cancer Prevention and Research Institute of Texas (CPRIT) Scholar in Cancer Research.

Breast cancer research has recently gotten a significant boost from precision medicine. In December 2020, a team from Scripps Research developed a tool that focuses on RNA to accelerate the development of precision medicine treatments for incurable diseases, including a type of metastatic breast cancer.

“It allows us to tackle very hard molecular recognition problems to enable us to make lead medicines across multiple indications,” said Matthew Disney, PhD, of Scripps Research. “This opens great potential to redefine what’s truly ‘undruggable.’”