Pancreatic cancer is one of the deadliest cancers in the world. Only about 13 out of every 100 people with this disease survive for five years after being diagnosed. This low survival rate is mostly because there are very few effective treatments. The most common type, called pancreatic ductal adenocarcinoma, is especially hard to treat.
One of the main reasons pancreatic cancer is so difficult to fight is because the tumor is not made up of just cancer cells. In fact, for some patients, only about 10% of the tumor is actually cancer. The rest is made up of other types of cells, which creates a tough environment for treatment.
These cancer cells are also cut off from blood vessels, which means they don’t get nutrients in the usual way. Instead, they adapt by finding new ways to survive—like recycling materials inside the cell, using special transporters to grab nutrients, and hiding from the immune system.
A new study from scientists at the University of Michigan, published in the journal Nature, brings new hope. The researchers discovered that targeting two specific molecules at the same time—called PIKfyve and KRAS-MAPK—can completely eliminate pancreatic tumors in mice and human-like models.
PIKfyve is an enzyme that plays a big role in how cells break down and recycle materials. It helps the lysosomes, which are parts of cells that act like trash collectors, to recycle and reuse fats. Although PIKfyve has been studied in other cancers, such as blood cancers, it wasn’t clear how it worked or whether it could help in pancreatic cancer.
The scientists used special genetically modified mice for their research. They found that mice missing the PIKfyve gene developed fewer tumors than normal mice. They also tested two drugs, apilimod and ESK981, that block PIKfyve. After 10 weeks, the mice treated with these drugs had much less cancer growth.
To understand how these drugs work, the researchers studied human pancreatic cancer cells in the lab. They found that when PIKfyve is blocked, lysosomes cannot recycle fats properly. As a result, the cancer cells are forced to make fats on their own. This switch turns on another set of genes that are controlled by the KRAS-MAPK pathway.
KRAS is known as the “master switch” in pancreatic cancer. It tells cells to grow and divide. New medicines that block KRAS are already being tested in clinical trials. But even though these KRAS-blocking drugs work at first, the cancer often becomes resistant over time.
That’s why the combination of targeting both PIKfyve and KRAS is so powerful. By blocking both at once, the cancer has fewer ways to fight back. In fact, in some of the best preclinical models available, this combination treatment completely wiped out the cancer in mice.
This research offers a new way to treat pancreatic cancer by attacking how cancer cells use fats and energy to stay alive. The team believes this new strategy could make current KRAS drugs work even better.
The scientists are now trying to figure out how to get rid of the few cancer cells that survive this treatment. They think that bringing in the immune system to help may be the final step to fully cure the disease.
Although this treatment has only been tested in lab and animal models so far, the results are very promising. If the same results can be achieved in humans, this could lead to a major breakthrough in the fight against one of the hardest cancers to treat.
If you care about cancer risk, please read studies that exercise may stop cancer in its tracks, and vitamin D can cut cancer death risk.
For more information about cancer, please see recent studies that yogurt and high-fiber diet may cut lung cancer risk, and results showing that new cancer treatment may reawaken the immune system.
The research findings can be found in Nature.
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