In a new study, researchers found that pancreatic cancer metastasis—when tumor cells gain the deadly ability to migrate to new parts of the body—can be suppressed by inhibiting a protein called Slug that regulates cell movement.
They also found two druggable targets that interact with Slug and hold promise as treatments that may stop the spread of pancreatic cancer.
The research was conducted by a team at Sanford Burnham Prebys Medical Discovery Institute and elsewhere.
Pancreatic cancer cells are notorious for their ability to escape from a tumor.
Even when pancreatic cancer is caught early, tumor cells are already found circulating throughout the body.
Once pancreatic cancer metastasizes, the number of people who are alive five years later drops from 37% to only 3%.
Pancreatic cancer cells, like all cancer cells, grow rapidly and quickly deplete the nutrients in their surrounding environment.
To meet their energy needs, tumor cells boost metabolic pathways that normal cells don’t use.
The team focused on the most commonly depleted nutrient, glutamine with the goal of finding treatments that stop the growth of cancer cells without harming healthy cells.
In the study, they used a mouse model of pancreatic cancer to show that, in response to glutamine deficiency, a protein called Slug drives metastasis by activating the epithelial-mesenchymal transition, or EMT—the process cells use to free themselves from tightly packed tissue.
Inhibiting Slug reduced cancer’s ability to spread—demonstrated by a reduction in the number and size of secondary lung tumors.
The scientists also showed that patient samples with higher levels of Slug were linked to a poor prognosis—further indicating that blocking the protein may be beneficial.
The study suggests that we may be able to create treatments that stop pancreatic cancer cells from untethering in the first place, which could reduce metastasis and help more people survive this deadly cancer.
Now that the researchers have established the important role of Slug in driving metastatic pancreatic cancer, they plan to expand their research to determine Slug’s role in pancreatic cancer overall, including the impact on disease aggressiveness and survival.
One author of the study is Cosimo Commisso, Ph.D., an associate professor in Sanford Burnham Prebys’ NCI-designated Cancer Center.
The study is published in the Journal of Experimental Medicine.
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