Halt cell recycling to treat cancer

Recycling cans and bottles is a good practice. It helps keep the planet clean.

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

Targeting and changing this process has been linked to helping control or diminish certain cancers. Now, University of Cincinnati researchers have shown that completely halting this process in a very aggressive form of breast cancer may improve outcomes for patients one day.

These results are published in the Feb. 8 print edition of the journal Developmental Cell.

a microscopic image showing autophagy in tumor cells

First image (left): Green marks the HER2 protein on the tumor cell surface, which drives breast cancer development and growth of tumor cells. Image two and three: After blocking the cell recycling process, known as autophagy, by eliminating the genes that cause it, HER2 is prevented from reaching the cell surface and accumulates in fluid-filled pouches, called vesicles (white arrows) and is eventually released from cells, stopping tumor cell growth. Provided by Guan’s lab

“Autophagy is sort of like cell cannibalism,” says corresponding author Jun-Lin Guan, PhD, Francis Brunning Professor and Chair of UC’s Department of Cancer Biology. “They eat the nasty components of themselves and come out strong and undamaged; however, we do not want cancer cells doing this to create stronger, healthier versions of themselves. Previous studies found that disabling this process slowed down the growth of another type of breast cancer, but it was unknown whether blocking autophagy could be beneficial for a particularly aggressive type of breast cancer, known as HER2-positive breast cancer.”

This type of breast cancer grows rapidly, and while there are effective treatments, unfortunately, these particular cancer cells find a way to become resistant to therapy, leading to relapse and a higher death rate in patients.

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 in other types of breast cancer,” says Guan, also a member of the UC Cancer Center.

“It would be harder for the cancer cells to develop ways to evade two different ways to be blocked,” he adds. “Future clinical studies will be needed to validate the treatment in human patients. Also, the HER2 protein plays a role in several other cancers including lung, gastric [stomach] and prostate cancers, so future studies will need to examine whether this new mechanism may also be beneficial in treating those cancers as well.

“This study really shows the value of basic research in beating cancer in the future. Breakthroughs, like this one, are sometimes made from curiosity-driven research that result in surprising findings that could one day help people.”

This research was funded by the National Institutes of Health (R01 CA211066; R01 HL073394; R01 NS094144). Researchers cite no conflict of interest.

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