Stopping cell recycling could help treat HER2-positive breast cancer

It is good practice to recycle cans and bottles. It helps keep the planet clean.

The same goes for recycling within the cells of the body. Each cell has a way of cleaning up waste in order to regenerate newer, healthier cells. This “cell recycling” is called autophagy.

Targeting and modifying this process has been linked to helping control or reduce certain cancers. Now researchers at the University of Cincinnati have shown that stopping this process altogether in a very aggressive form of breast cancer may improve patient outcomes one day.

These results are published in the February 8 print edition of the journal Development cell.

Autophagy is a bit like cellular cannibalism. They eat the nasty components of themselves and come out strong and undamaged; However, we don’t want cancer cells to do this to create stronger, healthier versions of themselves. Previous studies have shown that turning off this process slows the growth of another type of breast cancer, but it was not known whether blocking autophagy could be beneficial for a particularly aggressive type of breast cancer, known known as HER2-positive breast cancer. “

Jun-Lin Guan, Ph.D., Corresponding Author, Professor Francis Brunning and Head of the Department of Cancer Biology at UC

This type of breast cancer grows rapidly, and while there are effective treatments available, unfortunately these particular cancer cells find a way to become resistant to treatment, resulting in relapse and higher death rates in female patients.

The researchers in this study used animal models to show that blocking autophagy eliminated the development and growth of this type of breast cancer “even to a greater extent than our previous studies of other types of cancer. breast, ”says Guan, also a member of the UC Cancer Center.

He adds that the researchers also found that by blocking this activity, they could have a full impact on other activities and mechanisms within cancer cells, changing their roles and responses.

“This changed the trafficking patterns of the HER2 protein after it was produced by cancer cells,” he continues. “Instead of being placed in its ‘normal’ location on the cell surface to cause cancer to grow, it is incorporated into small, fluid-filled pockets called vesicles and secreted by tumor cells.”

Guan says these findings are particularly important because they show a completely different way of potentially treating this type of breast cancer and may work as a combination therapy with current treatments to prevent resistance and relapse.

“It would be more difficult for cancer cells to develop ways to avoid two different ways of being blocked,” he adds. “Future clinical studies will be needed to validate the treatment in human patients. In addition, the HER2 protein plays a role in several other cancers, particularly pulmonary and gastric. [stomach] and prostate cancers, so future studies will need to examine whether this new mechanism may also be beneficial in the treatment of these cancers.

“This study really shows the value of basic research in beating cancer in the future. Breakthroughs like this are sometimes made from curiosity-driven research that leads to startling discoveries that may one day help. people.”

Lead author of the study Mingang Hao, PhD, who is a postdoctoral fellow in Guan’s lab, says he was running two separate cancer research projects at the same time, but this study inspired the results of the study. other, which also involved vesicles or “bubbles”. in the spread of cancer.

“Cancer research has so many complex twists and turns, but much of it can be interconnected, even in tiny ways,” Hao says. “Working with the UC teams has shown me some really innovative ways to fight this disease, and I’m able to apply the things I learn in one lab to research in another, ultimately helping to find solutions to this terrible disease. “

Co-author Kevin Turner, MD, resident in UC’s Department of Surgery, says his work with this science is helping it better understand how cancer develops and spread to better treat patients.

“As a surgical resident planning to pursue a career in surgical oncology, having the opportunity to work in a scientific laboratory with Dr. Guan and his team has allowed me to develop a deeper understanding of how a disease works than I’ve seen in my patients, “he says.” I hope to continue studies on this as we work on clinical trials and apply it to patients.