Reducing RAGE for better health

When you’re studying a subject as complex as cancer, the most effective approach is often a multifaceted one. Bioengineering professor Wawrzyniec Dobrucki is leading an academically diverse team of researchers on a mission to help prevent and manage prostate cancer through an innovative pairing of biomarker detection and diet, and they are optimistic about the broader impact their research will have.

Inspiration and RAGE

It started with RAGE (receptor for advanced glycation end products). RAGE causes inflammation when it is activated by certain other elements in the body, called advanced glycation end-products (AGEs) and can lead to health problems as a result. Dobrucki had been studying RAGE before he joined the University of Illinois, but it was only after he began working at UIUC that he began to consider what the relationship between RAGE and cancer might be. After a thorough systematic review and meta analysis, his team established that detecting certain high amounts of RAGE can predictably indicate advanced prostate cancer.

The next step was to put this knowledge into practical use. Knowing that high levels of RAGE are connected to cancer, how could doctors and bioengineers use that knowledge to better identify tumors and other malignant growths? The team began studying the bioimaging potential of RAGE, and recently published a paper on their findings.

Based on their research, Professor Dobrucki’s team is optimistic that using medical imaging and peptide-based imaging probes to detect RAGE levels and the corresponding molecular changes within the tumor will not only be able to accurately identify potentially malignant tumors, but can do so more quickly and effectively than these traditional methods.

“The ultimate goal is that patients will be able to go to an imaging facility and the doctor can then use imaging to establish whether the patient has an overexpression of RAGE, which may indicate some important molecular changes in the prostate,” said Dobrucki. “That patient can then receive individualized treatment for malignant tumors faster than they would otherwise.”

In an effort to make this method of cancer detection more accessible, the team is hoping to make these peptide probes more widespread. Visualizing RAGE in cancer is not widely studied–in fact, the team at UIUC is one of three groups in the United States who can image it–which means there’s a lot of potential for improving medical information and cancer diagnoses once this detection method is put into practice. 

While the initial studies were conducted on prostate cancer, Dobrucki is optimistic that RAGE can be used to identify other types of cancer as well.

“We have more work to do in the area, but we have been able to confirm that breast cancer also expresses RAGE and the levels of RAGE are directly related to the severity of the disease,” Dobrucki said. 

What your diet can do for you

While RAGE is present in the same areas as cancer, it’s not necessarily the cancer cells alone that increase RAGE levels. RAGE levels increase when other elements in the body overexpress or over-activate the receptor and cause inflammation, which can then progress to cancer or other health issues linked to chronic inflammation like diabetes and hypertension. 

In their efforts to promote preventative cancer treatments, Dobrucki and his team were also interested in determining what elements might cause an increase in RAGE, inflammation, and related cancer risks. The team soon discovered that the foods we choose to eat and the way we prepare them hold some of the answers. 

“We did preliminary studies with mice bearing prostate tumors in which we gave one group a normal diet, and the other group a normal diet that we baked,” said postdoctoral researcher and research team member Catherine Applegate. “Baking produces lots of AGEs, which are absorbed by the body after being consumed and then go on to activate RAGE throughout the body. The mice that ate the baked diet rich in dietary AGEs had significantly higher levels of RAGE in their prostate tumor tissues and developed much more aggressive disease.”

Processed foods and fried foods are responsible for even higher levels of the receptor because food processing and heating to high temperatures leads to the development of these pro-inflammatory dietary AGEs, but Applegate, who is a registered dietitian nutritionist, was quick to point out that this doesn’t mean people should stop eating all foods prepared a certain way. While it is important to limit processed and fried foods in particular, a good general rule is to be mindful of what we eat, and keep our diet varied.

“It's important to have a variety of different foods cooked by a variety of different methods,” she said. “The process of cooking food isn’t bad. For example, there’s something in tomatoes called lycopene, which has anti-inflammatory benefits. But the lycopene in a raw tomato is not bioavailable; we can't absorb it when we eat a raw tomato. However, if you cook that tomato, the process releases the lycopene and we can absorb it. As little as a tablespoon of tomato paste per day can decrease the risk of developing prostate cancer by up to 30%!”

In addition to improving how cancer is detected, one of the team’s ultimate goals for this project is to create a set of dietary recommendations for patients with cancers expressing high levels of RAGE that will improve cancer outcomes by limiting intake of dietary AGEs. While those recommendations are not yet available, Applegate’s general advice for those interested in eating healthier (and with less RAGE) is to follow a dietary pattern similar to the Mediterranean diet when possible and follow the Dietary Guidelines for Americans. These guidelines recommend eating meals that are half fruits and vegetables and include some whole grains, some lean protein, and to limit saturated fats and added sugars. 

The research team’s interdisciplinary approach to tackling cancer has led to exciting findings with potentially far-reaching effects and cancer treatment improvements, as well as being a rewarding experience for the researchers.

“This research is my passion,” Dobrucki said. “In all these studies, I can see a direct translation to how prostate cancer patients can be better helped. And we're not talking about 20 years in the future–these changes can happen soon.”