Breast cancer is one of the most common cancers affecting women around the world.
Although treatments have improved greatly over the past few decades, breast cancer still causes many deaths each year, especially when the disease spreads to other organs. Doctors call this spreading process metastasis, and it is one of the biggest reasons cancer becomes difficult to treat.
Older adults often experience worse outcomes from breast cancer compared to younger patients. Scientists have known this for many years, but they have not fully understood why aging appears to make the disease more dangerous.
Now, researchers at Georgetown University’s Lombardi Comprehensive Cancer Center believe they may have found an important piece of the puzzle.
Their new study points to a protein receptor called RAGE, short for Receptor for Advanced Glycation End-products. The researchers discovered that aging may activate this receptor in ways that increase inflammation and help breast cancer spread more easily through the body.
The findings were published in the journal Communications Biology and will also appear in a special Nature collection focused on cancer and aging.
The research was led by Dr. Barry Hudson, associate professor of oncology at Georgetown Lombardi.
Scientists have long suspected that aging changes the body in ways that influence cancer growth. However, most cancer studies are traditionally performed using young laboratory mice. This means researchers may miss important biological changes that happen in older bodies.
Interestingly, this new study benefited from an unexpected situation during the COVID-19 pandemic. Because laboratory activity slowed down during the pandemic, some groups of mice aged much longer than originally planned.
This created a rare opportunity for researchers to compare cancer behavior in young and old mice directly.
The scientists used three different mouse models of triple-negative breast cancer, one of the most aggressive forms of breast cancer. Triple-negative breast cancer is particularly dangerous because it tends to grow quickly and has fewer treatment options compared to other forms of breast cancer.
The researchers found that older mice developed far more lung metastases than younger mice, even though the original tumors grew at similar rates in both groups. This suggested that aging mainly affected the ability of cancer to spread rather than simply increasing tumor growth.
The team then focused on RAGE. This receptor sits on the surface of cells and is known to increase inflammation inside the body. Chronic inflammation has already been linked to many age-related diseases, including diabetes, heart disease, Alzheimer’s disease, and cancer.
When the scientists genetically removed RAGE from the mice, the dramatic increase in metastasis seen in older animals almost completely disappeared. This strongly suggested that RAGE plays a major role in helping cancer spread during aging.
The researchers also found that aging increased levels of inflammatory proteins called S100 and HMGB1. These proteins activate RAGE and were found in both the primary tumors and the areas where cancer had spread.
According to the researchers, these inflammatory changes appear to create a body environment that helps cancer cells invade nearby tissues and move to distant organs more easily.
Dr. Hudson explained that aging does not simply increase cancer risk by chance. Instead, aging may actively change the body’s immune system and inflammatory pathways in ways that support tumor spread.
The researchers also wanted to see whether the findings might apply to humans. To investigate this, they analyzed breast cancer data from more than 1,000 patients.
The results showed that patients with higher levels of the AGER gene, which produces the RAGE receptor, tended to have worse outcomes. Higher levels of inflammatory gene activity linked to RAGE were also associated with poorer survival.
This finding strengthens the possibility that the same biological process may occur in human breast cancer patients.
The study also explored a possible treatment approach. Researchers tested a drug called TTP488, also known as azeliragon, which blocks RAGE activity. The drug has already been studied for other age-related diseases.
In laboratory experiments, TTP488 reduced the ability of breast cancer cells to become invasive when exposed to blood samples from older mice. This suggests the drug may help block some of the harmful effects of aging-related inflammation.
A clinical trial is already underway at Georgetown Lombardi to evaluate TTP488 in breast cancer patients receiving chemotherapy. Researchers are especially studying the drug’s safety and possible effects on cognitive function.
The scientists say the drug has shown a favorable safety profile so far, making it a promising candidate for future studies.
The research highlights a growing understanding in cancer science that tumors are not controlled only by mutations inside cancer cells. The surrounding environment inside the body also plays a major role.
Factors such as aging, inflammation, immune system changes, and metabolism may strongly influence whether tumors remain localized or spread to other organs.
If you care about breast cancer, please read studies about a major cause of deadly breast cancer, and this daily vitamin is critical to cancer prevention.
For more information about cancer, please see recent studies that new cancer treatment could reawaken the immune system, and results showing vitamin D can cut cancer death risk.
Source: Georgetown University.
