Doctors have discovered a new marker of one of America’s deadliest cancers – opening up the opportunity for early diagnosis and treatment.
Researchers at the University of California – San Diego looked at mice who were genetically engineered to mimic the early stages of pancreatic cancer, which kills nearly nine in 10 patients within five years.
Looking at cells under a microscope, they found cell stress and inflammation could be early warning signs of the disease as it can cause cancer cells to activate the protein STAT3, which has been shown to help tumors survive and resist treatment.
STAT3 then turns on the protein Integrin β3 (ITGB3) in mouse and human cells, which fuels the growth of pancreatic ductal adenocarcinoma (PDAC), the most common form of pancreatic cancer.
This causes PDAC to spread faster and become more difficult to treat.
Inflammation and cellular stress cause by chemotherapy also activated STAT3, increasing ITGB3 expression and further spreading the disease.
Based on the findings, researchers believe blocking STAT3 could stop tumors from forming while pancreatic cancer is still in its early stages.
Because most pancreatic cancers are only diagnosed after they have already spread, this could improve the overall survival rate.
Ryan Dwars of Iowa (left) and Holly Shawyer of North Carolina were both diagnosed with pancreatic cancer
David Cherish, study author and pathologist at UC San Diego, told Newsweek: ‘Given the fact that STAT3 plays such an important role in many cancers and the fact that it controls so many genes prompted us to drill down on which genes in particular are associated with cancer development, progression and drug resistance.’
The team also noted the findings could lead to early treatments fo lung, breast and skin cancers.
Pancreatic cancer affects roughly 67,000 Americans every year and kills about 52,000.
More than half the time, the disease is first spotted after it has already reached stage three or four due to its vague symptoms. These include abdominal pain, weight loss, back pain, jaundice and floating or clay-colored stools.
This leads patients to assume their symptoms are from more benign causes like irritable bowel syndrome (IBS).
By the time it reaches stage four, the five-year survival rate is just three percent, making it virtually incurable.
It’s unclear exactly what causes pancreatic cancer, but smoking, obesity and diabetes are thought to increase the risk by inducing harmful inflammation that causes cells to divide and become mutated more easily.
In the new study, published Tuesday in the journal Cell Reports, researchers genetically engineered mice to have a mutation in their KRAS gene, which raises the risk of lung, colorectal and pancreatic cancers.
This was done to help mimic early pancreatic cancer in humans.
The team found in the presence of inflammatory proteins and stress induced by low oxygen levels – which makes cancer cells more invasive and treatment resistant – STAT3 activates ITGB3 in both mouse and human pancreas cells, which accelerates the growth of pancreatic cancer cells.
This created a harmful loop between STAT3 and ITGB3, which caused tumors to become more aggressive and spread more easily.
The chart shows survival rates for pancreatic cancer, per the National Cancer Institute
Early signs of pancreatic cancer include jaundice, stomach pain, back pain and floating stools
However, when researchers used cancer drugs to target STAT3 early, cancer development slowed and became less aggressive, keeping it from spreading to other organs and becoming more difficult to treat.
In total, STAT3 induces the expression of 10 genes, including ITGB3, which form a gene signature the researchers dubbed ‘STRESS UP.’
The team believes detecting the STRESS UP signal early can help predict whether precancerous cells will turn into pancreatic cancer and determine how aggressive a tumor may become.
Cheresh said: ‘Having knowledge of this gene signature in patients could be valuable since there are known drugs on the market for other diseases that block STAT3 activation and thereby inhibit the expression of the STRESS UP genes in cancer cells.’
He noted STRESS UP could be used to help develop early screening tools for pancreatic cancer, as there is currently no way to test for it until symptoms develop.
The team now plans to explore molecules that could stop inflammation from activating ITGB3 not only in pancreatic cancer but also other forms of the disease that can affect the surface of tissues. These include lung, breast and skin cancers.
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