New Pathway Promising for Pancreatic Cancer

Not only is there no cure for pancreatic cancer, but there are currently no effective treatments. New findings may change this if new research keeps showing potential, according to investigators at the Mayo Clinic.

The researchers have found a major molecule that controls the growth, metastasis, and survival of pancreatic cells. This is a crucial first step toward devising new and better treatments for patients with pancreatic cancer. "This is a very exciting--and surprising--finding,” said Daniel Billadeau, Ph.D., a researcher from the Mayo Clinic (Rochester, MN, USA), and lead author of the study, published in the March 15, 2005, issue of the journal Cancer Research.

To find new target molecules with possibly therapeutic applications for a cancer for which there is currently no really effective treatment is very important. "Based on the literature, you would predict the opposite of what we found. But in fact, we determined that we can decrease a known regulator of cancer cell survival--in effect, turn this regulator off--and when we do, the pancreatic cancer cells undergo apoptosis [cell suicide] and die,” said Dr. Billadeau.

With this discovery, a new pathway has been created for researchers to target these key molecules that trigger pancreatic cancer growth. These findings may be used to make pancreatic cells more sensitive to gemcitabine, the only drug available for treating pancreatic cancer. This study may also lead to new drug development planning for other cancers. Further studies will define whether these same molecules play a similar role in the metastasis in other types of cancers.

The investigators found a previously unknown role in pancreatic cancer for the GSK-3 beta molecule. They found out that GSK-3 beta is vital to pancreatic cancer cell survival and growth through its effects in a well-known gene regulator called NF kappa B. This protein is well known to scientists as a transcription factor that regulates many genes. NF kappa B is hyperactive in many human cancers including pancreatic. This study demonstrated that in pancreatic cancer, the NF kappa B activity is regulated by GSK-3 beta.

Researchers determined this by demonstrating that if they could decrease GSK-3 beta protein or turn it off by using small molecular inhibitors, they could also decrease NF kappa B and deprive the pancreatic cancer cells of a way to grow and survive. Significantly, in pancreatic cancer, NF kappa B activity is high, which can cause resistance to chemotherapeutic agents used to treat the disease. This new research suggests a possible way to treat pancreatic cancer by a two-pronged attack of administering gemcitabine in combination with an agent to block GSK-3 beta.

Almost all patients (97%) with pancreatic cancer die within five years of diagnosis. Therefore, it is imperative that researchers welcome any possible leads for improving detection and therapy of this disease.


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