Stopping cell regeneration could treat HER2-positive breast cancer

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

The same is true for internal recycling of cells in the body. Each cell has a way to clean up waste to regenerate healthier cells. This “cell recycling” is called autophagy.

Focusing and modifying this process has been linked to helping control or reduce some cancers. Now, University of Cincinnati researchers have shown that stopping this process completely in the highly aggressive form of breast cancer could improve outcomes for patients one day.

These results are published in the February 8 issue of the journal Cell development.

Autophagy is very similar to cell cannibalism. They eat the bad parts of themselves and come out strong without damage; however, we do not want cancer cells to do this to create stronger and healthier versions of themselves. Previous studies have found that stopping this process slowed the growth of another type of breast cancer, but it was not known whether preventing autophagy would be beneficial for a particularly aggressive type of breast cancer. called HER2-positive breast cancer. “

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

This type of breast cancer grows rapidly, and while there are effective treatments, unfortunately, these specific cancer cells are finding a way to resist treatment, leading to relapse and higher mortality rate in patients.

Researchers in this study used animal models to show that inhibition of autophagy inhibited 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, said Guan, who is also a member of the UC Cancer Center.

He also said that researchers found that by inhibiting this activity, they were able to have a total effect on the actions and other mechanisms within the cancer cells, altering the roles and their reactions.

“It changed the trading patterns of the HER2 protein after it was secreted by the cancer cells,” he continues. “Instead of being placed in its‘ normal ’place on the surface of the cells to cause the development of cancer, it is absorbed into some small water-filled spouts, called vesicles, and released. out of the tumor cells. “

Guan says these findings are especially important because they show a completely different approach to treating this type of breast cancer and could work as a combination therapy. with conventional therapies to prevent stress and relapse.

“It would be more difficult for the cancer cells to develop ways to block two different ways,” he said. “Future clinical studies will be needed to confirm the treatment in human patients. In addition, the HER2 protein plays a role in several other cancers including lung, gastric [stomach] and prostate cancers, so future studies need to explore whether this new equipment may be beneficial in treating these cancers as well.

“This study certainly demonstrates the value of fundamental research in the future severity of cancer. Breaks, like this one, are sometimes made from curiosity-led research that yields amazing results. that could one day help people. “

The study’s lead author Mingang Hao, PhD, who is a postgraduate associate at Guan Laboratory, says he was handling two separate cancer research projects at the same time, but this study prompted results for the another, which also contained vesicles or “bubbles” in the spread of cancer.

“There are so many complex twists and turns in cancer research, but so much can be interconnected, even in tiny ways,” says Hao. “Working with the teams at UC in real ways show me innovative ways to deal with this disease, and I can apply things I learn in one laboratory to study in another, to help find solutions for this terrible disease. “

Co-author Kevin Turner, MD, a resident in the Department of Surgery at UC, says his work with this science is helping him understand more about cancer development and spread to better treat patients.

“As a surgical resident who intends to pursue a career in surgical oncology, I have the opportunity to work in a science laboratory with Dr. Guan and his team have given me the opportunity to gain a deeper understanding of disease functioning that I have seen in my patients. , “he says.” I hope to continue studies on this as we work towards clinical trials and its application in patients. “

Source:

Magazine Reference:

Hao, M., et al. (2021) Limitations of HER2 + Tumorigenesis Inhibition of breast cancer by disrupting HER2 trafficking and stimulating transmission through small extracellular viruses. Cell development. doi.org/10.1016/j.devcel.2020.12.016.

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