CSUN Prof Identifies New Approach for Targeting Breast Cancer Metastasis

Photo by Lee Choo

CSUN biologist Jonathan Kelber, above at the white board, has identified a new approach for targeting breast cancer metastasis.  

California State University, Northridge biologist Jonathan Kelber and a team of current and former trainees have identified a small molecule compound that, when delivered to breast cancer cells in animal models, can interfere with metastasis.

Metastasis is the process of cancer cells moving from their original site of growth to other tissues in the body through the blood stream and forming tumors elsewhere. It is what leads to over 95 percent of deaths resulting from solid tumor types (e.g., breast and pancreatic). The findings, Kelber said, represent an important step toward developing targeted treatment strategies for aggressive forms of cancer.

“We are still in the early stages of our research,” he said. “But, if what we have observed holds true in additional models, we may be able to develop this approach into a therapy that specifically goes after the unhealthy cells and has limited adverse effects on healthy cells.”

Their findings were published in the Nov. 19 issue of the scientific journal Biochemical and Biophysical Research Communications. In addition to Kelber, the research team was led by former CSUN postdoctoral student Robert Güth and former CSUN graduate student Yvess Adamian.

The molecule that Kelber’s research team identified is known as GC7, and when delivered to breast cancer cells growing in animals, it can act as a “decoy” to prevent the protein eIF5A from becoming activated and translating the PEAK1 gene, a critical cancer “support wall.” Thus, GC7 is able to block breast cancer cell metastasis. They’ve replicated these results across multiple mouse and human breast cancer cell types.

Kelber and his team were the first to show that PEAK1 is essential at the earliest stages of aggressive breast cancer metastasis, causing otherwise healthy cellular signals to become cancer-causing — a study that was published in 2015 in the Public Library of Science (PLoS) One Journal. In 2017, Kelber received a $1.46M R01-equivalent NIH SC1 grant for his lab to study mechanisms of PEAK1 function in normal and diseased tissues. His group has done similar research on the role that PEAK1 plays in pancreatic cancer progression.

Kelber said the use of GC7 to inhibit the metastasis of breast cancer — in particular, one of the hardest-to-treat forms, triple-negative breast cancer — could have implications for understanding and treating other cancers, as well.

“We know that PEAK1 plays a role in the development of pancreatic cancer, so it’s a logical step to hypothesize that GC7 could inhibit the metastatic spread of this cancer type also,” he said.

“We’re not at a stage where we can test this in humans yet, but our work appears to be very promising,” Kelber said. “We are now focusing on understanding how this all works, and in what specific contexts.”

One very interesting thing that the researchers discovered that may be a key mechanism of how GC7 works is that it seems to lock tumor cells into a specific cellular state — one that is not conducive to metastatic spread and renders the cells more susceptible to cell death.

“Ultimately, we want to develop therapies for triple-negative breast cancer that enable the survival of healthy cells, while simultaneously killing the unhealthy, cancerous cells,” Kelber said.

He noted that those diagnosed with triple-negative breast cancer have to undergo severe, toxic chemotherapy treatment regimens, with no guarantee of effectiveness. “The idea of pursuing potentially targeted therapy in these instances would be so much better for the patient,” he said.

The research was carried out entirely by CSUN trainees, including former and current lab members Megain Agajanian, Justin Molnar, Sa La Kim, Kayla Meade, Lindsay Kutscher, Kishan Bhakta, Joanna Maddela and Cameron Geller.

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