Illustration showing a pancreas with pancreatic cancer highlighted in red.

The protein called studying secreted frizzled-related protein 2 (SFRP2) that has long been known to be involved in tumor growth and angiogenesis in breast cancer and osteosarcoma could be a new pancreatic cancer treatment target. New findings, from the Medical University of South Carolina (MUSC) Hollings Cancer Center shows that SFRP2 is especially abundant in pancreatic cancer, and the more abundant it is, the worse the likely patient outcomes.

The research published in the journal Cancer Biomarkers, was led by MUSC researcher Nancy Klauber-DeMore, MD, who first began studying the role of SFRP2 as a breast cancer surgeon more than 15 years ago, and later expanded her inquiry of the protein’s role in cancer development to osteosarcoma. These new findings in pancreatic cancer indicate that so much SFRP2 is concentrated in the tumor itself and not in the surrounding tissue, that it is fertile target for future therapy development.

“Our next steps will be to see if by blocking SFRP2, we could affect the tumor,” Klauber-DeMore says. “We could potentially affect tumor fibrosis. We could affect angiogenesis. We could kill the tumor cells themselves, and we could also affect the immune system as immunotherapy. So, for those reasons, we have described SFRP2 as a potential biomarker and a potential therapeutic target for pancreatic cancer.”

Pancreatic cancer is the third most common cause of cancer death and may become the second most common cause of cancer death by the year 2030. One reason, the cancer it so lethal is that by the time it is diagnosed it has most often spread beyond the pancreas. Pancreatic tumors also grow a thick stroma of associated tissue that both inhibits the infiltrations of chemotherapy to kill the tumor, while also interacting with the tumor to promote its growth.

Prior attempts to treat the cancer have had mixed results indicating that more complete knowledge of all the elements affecting the growth of pancreatic cancer, and how the different element of tumor microenvironment communicate with each other to drive the disease are needed. Because SFRP2 aids in stroma production and preventing immune cells from recognizing and attacking the tumor, targeting SFRP2 could potentially have multiple effects on the tumor microenvironment.

Klauber-DeMore noted that her focus on the role of SFRP2 shifted to pancreatic cancer after querying the Cancer Genome Atlas looking for more information about the tumor growth protein.

“You can look at expression of a gene in all different types of human cancer, and when we put SFRP2 in, the cancer that had the highest expression was pancreatic cancer,” she said. “And so that’s the reason that we started looking to see if SFRP2 was a target in pancreatic cancer.”

She then saw that patients with high levels of SFRP2 had lower odds of survival. Her lab subsequently investigated how SFRP2 relates to KRAS, a gene that’s heavily involved in pancreatic cancer when it mutates.

“When we silenced KRAS, it greatly reduced the expression of SFRP2. So what this is saying is that KRAS, which is known to be one of the main drivers of pancreatic cancer, drives the expression of SFRP2,” Klauber-DeMore said.

Klauber-DeMore previously developed a humanized monoclonal antibody to SFRP2 that received rare pediatric disease designation from the U.S. Food and Drug Administration for osteosarcoma.

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