Researchers have discovered a protein that they believe makes pancreatic cancer “so deadly”.
Pancreatic cancer is the tenth most common form of the disease in the UK, with 28 patients being diagnosed every day.
The survival rate is high, with only 5% of cases still alive 10 years later.
A team from the Sanford Burnham Prebys Research Institute in San Diego has set out to reveal how pancreatic tumors would react if they starved of oxygen and expected to thrive.
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After shutting down a gene that causes oxygen deprivation for these malignant cells in mice, US researchers were surprised that the disease became more aggressive.
When they dug deeper, the team found that these rodents had higher levels of the protein PPP1R1B.
After removing the gene encoding this protein, the mice improved and raised hopes that PPP1R1B may be a new drug target.
The discovery “can help people fight the toughest cancer”
“Our study reveals a protein, called PPP1R1B, which is completely new to researchers in pancreatic cancer and which drives tumor metastasis, the main reason why the cancer is so deadly,” said study author Dr Anindya Bagchi.
“With this proof-of-concept information, we can launch drug screens that identify an inhibitor of PPP1R1B, which, if successful, can help more people survive pancreatic cancer.
Pancreatic cancer is notoriously difficult to treat. Patients tend to be diagnosed in the later stages of the disease because there is no screening program and the symptoms are generally vague, such as upper abdominal pain.
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The pancreas is also located near other vital organs, such as the liver and intestines, which increases the risk that a tumor will spread.
If the disease remains within the pancreas, the five-year survival rate in the United States is 37%.
The pancreas is considered a hostile environment, with cancer cells usually receiving some oxygen or nutrients.
Although you can expect the tumor to go away, it often thrives despite these difficult conditions.
Cancer researchers have long speculated that increased production of hypoxia-inducible factor 1 alpha (HIF1A), a gene triggered by low oxygen levels, stimulates tumor growth.
To learn more, Sanford researchers genetically engineered mice to have tumors in the pancreas, but do not produce HIF1A.
They thought that removal of this gene would allow mice to become cancer-free, but the rodents developed more aggressive tumors that invaded adjacent tissues and eventually killed the animals.
“Our original hypothesis was if we remove HIF1A, a putative driver of tumor survival, growth would be delayed or if we should cure cancer,” said Dr. Bagchi.
“Instead, we got exactly the opposite result.
“When we saw this, we knew we might have come across something really interesting and needed to nail down exactly why we see this effect.”
The researchers then discovered that these mice had increased levels of PPP1R1B.
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Results, published in the journal Gastroenterology, revealed that removal of the gene encoding this protein caused the tumors to spread less.
“Our data also showed tumor samples from people with metastatic pancreatic cancer had elevated levels of PPP1R1B, which adds further evidence that the protein has therapeutic potential,” said co-lead author Dr. Ashutosh Tiwari.
Elevated levels of PPP1R1B have also been found in colon, lung and prostate cancers and can also be seen in other hypoxic [low oxygen] tumors, so an inhibitor may have benefits in addition to pancreatic cancer. “
The researchers plan to screen drugs to identify compounds that inhibit PPP1R1B.
“The path to successful treatment of pancreatic cancer begins with a strong scientific understanding of what drives tumor growth and aggression,” said Dr. Lynn Matrisian of the Pancreatic Cancer Network.
“This study has discovered a promising drug target that, after further research, could one day lead to a treatment that will help more people fight the world’s toughest cancer.”