Scientists have discovered a possible reason why breast cancer often becomes more dangerous as people grow older.
New research from Georgetown University suggests that aging changes the body in ways that may help cancer spread more easily to other organs.
The study focused on a protein receptor called RAGE, which appears to increase inflammation inside the body and create conditions that help cancer cells survive and spread.
Researchers believe this discovery could eventually lead to new treatments aimed at slowing or preventing metastasis, the deadly process in which cancer moves beyond the original tumor.
The findings were published in Communications Biology and will also be featured in a special Nature collection on cancer and aging.
Breast cancer is one of the leading causes of cancer deaths in women worldwide. Many patients survive when the disease is detected early and remains limited to the breast. However, once cancer spreads to organs such as the lungs, liver, bones, or brain, treatment becomes much more difficult.
Doctors have noticed for many years that older patients often experience worse outcomes from breast cancer. However, scientists have struggled to explain exactly how aging changes the body to support cancer progression.
According to Dr. Barry Hudson, who led the study at Georgetown Lombardi Comprehensive Cancer Center, most cancer research has traditionally relied on young laboratory mice. As a result, researchers may have underestimated the importance of aging itself in shaping cancer behavior.
Unexpectedly, the COVID-19 pandemic created an unusual research opportunity. Because many laboratories temporarily slowed down during the pandemic, some groups of mice aged longer than researchers originally planned. This allowed scientists to directly compare cancer behavior in younger and older animals.
The team used three separate mouse models of triple-negative breast cancer, one of the most aggressive forms of the disease. Triple-negative breast cancer is especially difficult to treat because it does not respond to some common hormone-based therapies.
The researchers found that older mice developed far more lung metastases than younger mice, even though the original tumors grew at similar speeds. This suggested that aging mainly affected the cancer’s ability to spread rather than the size of the primary tumor itself.
The scientists then focused on RAGE, a receptor found on the surface of cells. RAGE is already known to play a role in chronic inflammation and several age-related diseases.
Inflammation is part of the body’s natural defense system, but long-term inflammation can become harmful. Chronic inflammation has been linked to heart disease, diabetes, Alzheimer’s disease, and many cancers.
The researchers discovered that aging increased levels of inflammatory molecules called S100 and HMGB1. These molecules activate RAGE and appear to help create a body environment that supports cancer spread.
To test how important RAGE was, the scientists genetically removed the receptor from mice. The results were dramatic. Without RAGE, the large increase in metastasis seen in older mice was almost completely eliminated.
This finding strongly suggests that RAGE acts as a major driver connecting aging, inflammation, and cancer spread.
The researchers also wanted to know whether the same pattern might exist in humans. They analyzed medical and genetic information from more than 1,000 breast cancer patients.
Patients with higher activity of the AGER gene, which produces the RAGE receptor, tended to have worse outcomes. Inflammatory gene patterns connected to RAGE were also associated with poorer survival.
The team then investigated whether blocking RAGE might reduce cancer aggressiveness. They tested a drug called TTP488, also known as azeliragon, which blocks RAGE signaling.
In laboratory experiments, the drug reduced the ability of breast cancer cells to invade tissues when exposed to blood samples from older mice. This suggests the drug may weaken some of the harmful inflammatory effects linked to aging.
Importantly, TTP488 has already been studied for other age-related conditions and appears to have a relatively favorable safety profile. Researchers are now conducting a clinical study at Georgetown Lombardi to evaluate the drug in breast cancer patients receiving chemotherapy.
Scientists believe this work highlights a broader lesson about cancer biology. Tumors are not influenced only by their own mutations. The body environment surrounding cancer cells also matters greatly.
As people age, the immune system, inflammation levels, and metabolism all change. These changes may create conditions that allow tumors to spread more easily.
The study also supports growing interest in targeting inflammation as part of cancer treatment. Rather than focusing only on destroying cancer cells directly, future therapies may also try to change the biological environment that helps tumors grow and spread.
If you care about breast cancer, please read studies about how eating patterns help ward off breast cancer, and soy and plant compounds may prevent breast cancer recurrence.
For more health information, please see recent studies about how your grocery list can help guard against caner, and a simple way to fight aging and cancer.
Source: Georgetown University.
