Pancreatic cancer is one of the deadliest cancers: Fewer than 10% of people with this type of cancer remain alive five years later.
The tumor is difficult to detect because symptoms often don’t appear until the disease has already metastasized.
However, if the tumor is contained in the pancreas, the five-year survival rate increases to nearly 40%, according to the American Cancer Society.
For unknown reasons, pancreatic cancer is on the rise and predicted to become the second-leading cause of cancer-related deaths in the U.S. by 2030.
In a recent study at Sanford Burnham Prebys Medical Discovery Institute, researchers found a novel drug target, a protein called PPP1R1B, that stops the deadly spread of pancreatic cancer, called metastasis.
The findings are the first step toward a potential treatment for one of the deadliest cancers known today.
The study is published in Gastroenterology. One author is Anindya Bagchi, Ph.D.
In the study, scientists set out to understand how pancreatic cancer responds to oxygen deprivation (hypoxia).
Cancer researchers have long wondered how pancreatic cancers are able to thrive in such a harsh environment—and speculated that increased production of HIF1A, a gene triggered by hypoxia, can stimulate tumor growth.
Drugs that inhibit HIF1A are being explored for many cancers, but until now the protein’s role in pancreatic cancer was unclear.
As a first step, the scientists created mice with pancreatic tumors that do not produce HIF1A.
They expected that removing this protein would be beneficial and allow the mice to become cancer-free.
However, to their surprise, these mice had more aggressive tumors—with more invasion into nearby organs, greater metastasis and shorter survival times.
Digging deeper, the scientists discovered that these mice had increased levels of a protein called PPP1R1B.
When they removed the gene that codes for this protein, the mice had fewer metastases—suggesting that a drug that inhibits the protein would stop pancreatic cancer from spreading.
The data also showed that tumor samples from people with metastatic pancreatic cancer had increased levels of PPP1R1B, adding further evidence that the protein has therapeutic potential.
Elevated levels of PPP1R1B have also been found in colon, lung, and prostate cancers, and might also be seen in other hypoxic tumors, so an inhibitor may have benefits beyond pancreatic cancer.
Next, the scientists plan to start drug screens that seek to identify compounds that inhibit PPP1R1B.
These activities will take place at the Institute’s Conrad Prebys Center for Chemical Genomics, one of the most advanced drug discovery centers in the nonprofit world.
The team says with this proof-of-concept data, they can start drug screens that identify an inhibitor of PPP1R1B, which, if successful, may help more people survive pancreatic cancer.
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