- A new study could help lead to new ways of treating pancreatic ductal adenocarcinoma (PDAC).
- Scientists have discovered a strong link between the protein SRSF1 and pancreatic cancer in mice.
- High levels of SRSF1 appear to cause inflammation or pancreatitis, which can lead to PDAC.
Pancreatic ductal adenocarcinoma (PDAC), the most common form of pancreatic cancer, is one of the most aggressive and lethal of all cancer types, and among the hardest to treat.
Chemotherapy is the primary systemic therapy used for pancreatic cancer.
Targeted therapy and immunotherapy are occasionally used in select individuals with specific molecular or genetic features, according to the American Society of Clinical Oncology (ASCO)
But more than 90% of people with PDAC die within five years of diagnosis.
A new finding, however, could lead to a new way of treating PDAC.
Scientists at Cold Spring Harbor Laboratory (CSHL) in Laurel Hollow, New York have discovered a strong link between the protein SRSF1 and pancreatic cancer in mice.
Professor Adrian Krainer, PhD at CSHL, who led the study, said his team zeroed in on SRSF1 and found that high levels of SRSF1 cause inflammation or pancreatitis.
This jumpstarts PDAC tumor development.
Krainer says that cells have several processes to keep SRSF1 levels constant, but cancer tends to find a way to overcome these checks and balances.
Several genes, RNAs, and proteins work together in cells to keep SRSF1 levels steady. But sometimes, the process gets disrupted. In the pancreas, this triggers pancreatitis and accelerates PDAC, he said.
“It’s a very pronounced effect,” Krainer explained in a press statement. “We could see that patients whose tumors express higher levels of SRSF1 have worse outcomes. So, we set out to explore to what extent SRSF1 contributes to PDAC.”
The team discovered that higher levels of SRSF1 are vital for PDAC growth in mice and organoids — which are small versions of tumors.
The organoids stopped growing when SRSF1 returned to normal levels.
While SRSF1 may not be an ideal drug target by itself because it is important in healthy tissue, this discovery is promising because some of the splicing changes SRF1 promotes may be able to be targeted instead.
A digestive cancer, pancreatic cancer starts when cells in the pancreas grow out of control, according to Scripps MD Anderson Cancer Center.
The pancreas is located behind the stomach and produces enzymes and hormones that help digestion and maintain healthy blood sugar levels.
A paper from the American Association for Cancer Research noted, “SRSF1 has been repeatedly surprising and intriguing investigators by the plethora of complex biologic pathways it regulates.”
Herve Tiriac, PhD, is an Assistant Research Scientist at UC San Diego Health in the Department of Surgery. He reviewed the data and believes it has the potential to help develop future pancreatic cancer treatments.
“This seems like a very interesting finding that could open a new avenue of investigation in pancreas cancer and potentially other malignancies,” he told Healthline. “Splicing is an essential regulatory element of our healthy cells and the dysregulation of splicing in pancreas cancer remains largely unexplored.”
Tiriac added, “This study lays the groundwork for future studies that will attempt to identify druggable vulnerabilities to kill pancreas cancer cells with aberrant splicing.”
The risk of developing pancreatic cancer in the United States is about 1 in 65, but an individual’s risk can be significantly affected by certain factors, including inherited gene mutations.
Usually, by the time the cancer is identified, it has already spread.
The American Cancer Society
“This shows that it can play an important role. There is not yet enough data, but we will keep studying this,” said Krainer, who added that if scientists can clearly understand the underlying genetic mechanisms of PDAC, this might lead to earlier diagnoses and new types of therapies.
Krainer and his team at CSHL — Postdoc Ledong Wan and CSHL Professor David Tuveson — will continue to explore the role of a genetic process called RNA splicing in pancreatic cancer.
“We’re excited by these developments,” Krainer said in a press statement. “But PDAC is a difficult and complicated malignancy. We’re hoping to provide actionable information for future treatments. This work spearheaded by Ledong is just the tip of the iceberg.”