Pancreatic cancer is one of the most deadly forms of cancer. The most common type is called pancreatic ductal adenocarcinoma, or PDAC. It is hard to treat and often becomes resistant to current therapies.
Most treatments today try to block a cancer-causing gene called KRAS. While this can help for a while, many tumors find ways to get around it. That’s why scientists are looking for new ways to treat this disease.
In 2023, researchers at Cold Spring Harbor Laboratory (CSHL) made an important discovery. They found that a protein called SRSF1 plays a key role early in the development of pancreatic cancer.
Now, a new team led by former CSHL student Alexander Kral has learned more about how this protein works. They found that SRSF1 is part of a larger system that helps cancer grow and become more dangerous.
This system involves three main parts: SRSF1, a molecule called AURKA (Aurora kinase A), and a well-known cancer gene called MYC. These three work together in a cycle that keeps the cancer going.
Here’s how it works: SRSF1 changes the way the AURKA gene is used by the body, through a process called alternative splicing. This causes the body to make more AURKA. In turn, AURKA helps protect the MYC protein, which is also involved in cancer. Then MYC boosts the levels of SRSF1 again. This forms a repeating loop that keeps the cancer alive and growing.
The researchers wanted to find a way to break this loop. They designed a special molecule called an antisense oligonucleotide, or ASO. ASOs are small synthetic strands of genetic material that can block or change how genes are used. The team has experience with ASOs—they previously helped develop Spinraza, the first drug approved to treat spinal muscular atrophy.
They created an ASO that would block the splicing of AURKA. At first, they thought it would simply lower AURKA levels. But in pancreatic cancer cells, something surprising happened. The treatment caused the entire cancer-supporting system to collapse. The tumor cells could no longer survive, and they began to die through a natural process called apoptosis.
Dr. Adrian Krainer, the lead researcher, described it as “killing three birds with one stone.” By targeting just AURKA, the levels of all three cancer-related proteins—SRSF1, AURKA, and MYC—went down.
This finding is exciting because it suggests that blocking just one part of the system can shut down the whole cancer process. The ASO targets AURKA, but it ends up affecting the other two proteins as well.
Right now, this treatment is only being tested in labs, not in people. But the researchers are working to improve it. They hope that one day, this approach could lead to a new kind of therapy for pancreatic cancer.
Although it may take years before this becomes a treatment used in hospitals, it is a promising step forward. Just like Spinraza began as a small discovery and later helped thousands of people, this research could eventually save lives. It shows how deep scientific work can lead to new hope for people with hard-to-treat cancers.
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The study is published in Molecular Cell.
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