Cancerwise

There’s a delicate balance that’s required when it comes to inflammation and your health. Without it, your body would never heal from an infection or injury. But too much can lead to other health issues. As we age, the chance of experiencing inflammation increases, and naturally, this can lead to more inflammation-related diseases, like cancer.

Rugang Zhang, Ph.D., Experimental Therapeutics chair, runs a lab at UT MD Anderson that dedicates much of its work to understanding the relationship between aging, inflammation and inflammation-related diseases, including cancer. He says the bond between aging and inflammation is so strong that scientists have come up with a new term for it: inflammaging.

We spoke with Zhang to learn more.

What is inflammaging?

Inflammation is the immune system’s response to injury or infection. It’s necessary for healing. But inflammation without injury or infection can be harmful and cause chronic diseases, like osteoarthritis or cancer.

Inflammaging is the chronic inflammation that develops throughout the body as we age and get older. It gradually damages cells and tissues and actually accelerates the aging process, leading to some of those chronic diseases I mentioned before.

What’s the link between inflammaging and our health?

Inflammaging causes cells to malfunction. It wears down the immune system, slowing its ability to respond to new stressors. It rewires the metabolism. All of this leads to more age-related diseases.

How can a deeper understanding of inflammation and aging lead to advances in cancer treatment?

Since we know inflammaging – and inflammation in general – can promote cancer, improving our understanding could eventually lead to new ways to treat inflammation, and stop or slow it from progressing, or stop it from causing cancer and other diseases.

My lab has been looking at what happens to cells as they age. They stop dividing and enter a state we call senescence. That’s when inflammation starts based on the signals the cells send. Up until now, our understanding of these signals was incomplete. My team recently uncovered that a change is tied to nucleic acid structures made out of RNA and DNA called R-loops.

Normally, you can find R-loops in the cell nucleus, but in senescence R-loops are exported into the cytoplasm, the fluid between the cell membrane and the nucleus, and this triggers the inflammatory response. It’s a process that creates widespread, chronic inflammation and it won’t turn off, and it’s all thanks to two proteins that cause the R-loops to exit the nucleus and enter the cytoplasm.  

One of those proteins is called XPO-1. My lab was aware of a targeted therapy drug called KPT-330 that blocks XPO-1. It was already approved by the Food and Drug Administration and used to treat some types of lymphoma and leukemia. We tested this drug and found that in preclinical models it suppressed inflammaging. Along with that, it lowered systemic inflammatory markers, reversed age-related body composition changes and collectively extended health span. This discovery paves the way to explore specific means to block R-loop nuclear exit to treat age-related conditions besides cancer, possibly including dementia and Alzheimer’s disease.

Deepening our understanding of inflammaging and cancer will help unlock new treatments for not just cancer, but other age-related diseases. It’s an exciting time to be conducting research in this field. We’ve unlocked some key understandings in recent years, and I can’t wait to see what we develop next and how it drives breakthroughs for cancer patients and aging populations.

Learn about research careers at UT MD Anderson.