Pancreatic cancer is one of the deadliest forms of cancer because it is often found only after it has already spread to other parts of the body.
Once this happens, treatment becomes much more difficult and survival rates fall sharply. Scientists have spent many years trying to understand how pancreatic cancer cells leave the pancreas, survive in other organs, and continue growing.
A new study from the University of California, San Francisco (UCSF) has uncovered an important clue that could one day lead to better treatments.
The research, published in the journal Nature, focused on a protein called PCSK9. While this protein is already known for helping control cholesterol in the body, the researchers found that it also plays an important role in helping pancreatic cancer cells adapt to different organs after they spread.
To make the discovery, the scientists used information from a research project called MetMap, which follows how cancer cells move throughout the body.
They studied pancreatic cancer cells that commonly spread to either the liver or the lungs. The goal was to understand why some cancer cells settle in one organ while others grow somewhere else.
The team found that cholesterol plays a major part in this process. Cholesterol is a natural fatty substance that every cell needs to build membranes and carry out many important jobs. Different organs contain different amounts of cholesterol. The liver is rich in cholesterol, while the lungs have much lower levels.
The researchers discovered that pancreatic cancer cells with low amounts of PCSK9 could absorb cholesterol directly from the liver after they arrived there. However, cancer cells with high levels of PCSK9 behaved very differently. Instead of relying on cholesterol from the surrounding tissue, they produced their own cholesterol and made extra molecules that helped them survive in the lungs, where oxygen levels are higher and the environment is more stressful.
One of the study’s most surprising findings came when the scientists changed the amount of PCSK9 inside pancreatic cancer cells. Liver-seeking cancer cells that were genetically altered to produce more PCSK9 no longer preferred the liver. Instead, they began spreading to the lungs. This showed that PCSK9 does more than simply identify where cancer cells may grow. It actively changes their behaviour and helps them adapt to new conditions.
The researchers believe this discovery could open the door to new ways of treating pancreatic cancer. If future medicines can block or control PCSK9 inside cancer cells, doctors may be able to reduce the ability of the disease to spread to distant organs. Preventing or slowing the spread of cancer is one of the biggest challenges in cancer treatment because metastatic disease is responsible for most cancer-related deaths.
Although these findings are very encouraging, the scientists emphasise that more research is still needed before patients can benefit from this approach. Future laboratory studies and clinical trials will be needed to confirm whether targeting PCSK9 is safe and effective in people with pancreatic cancer.
This work was supported by organisations including the National Institutes of Health and the National Science Foundation, highlighting the importance of developing better treatments for this devastating disease.
The study also reminds us that understanding how cancer cells use nutrients such as cholesterol may reveal entirely new ways to fight cancer. While this research is still in its early stages, it offers fresh hope that future therapies may stop pancreatic cancer before it spreads and becomes much harder to treat.
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