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Turning the Corner in Cancer Treatment
CHORI Scientists Identify Novel Target for Cancer Treatment

November, 2011 - Two recent publications by CHORI scientists demonstrate the viability of a newly discovered sugar molecule, called de-N-acetyl sialic acid or neuraminic acid containing polysialic acid (NeuPSA), as a potential target for cancer-fighting vaccines and drugs. In the Journal of Biological Chemistry, CHORI scientist Gregory R. Moe, PhD, and his colleagues illustrate that NeuPSA is expressed in both normal human and cancer tissues, while in the second paper, just out in the November 9th issue of PLoSOne, they show that antibodies directed against NeuPSA can cause cell death.

“NeuPSA appears to have a much broader role in human biology than previously recognized,” says Dr. Moe. “Targeting the NeuPSA pathway with vaccines, antibodies, and drugs offers many possible new approaches to preventing and treating cancer in humans.”

“Targeting the NeuPSA pathway with vaccines, antibodies, and drugs offers many possible new approaches to preventing and treating cancer in humans.”



Dr. Moe and his colleagues first discovered NeuPSA while working on vaccine development for bacterial meningitis. NeuPSA is a derivative of polysialic acid (PSA), which is the capsular polysaccharide of Neisseria meningitidis group B bacteria.

"The main purpose of PSA is to allow cells to move around without sticking to anything. It is made in the largest amounts during fetal development," explains Dr. Moe. "On the other hand, PSA as a whole was thought to exist in adults in only a few areas of the brain and in leukocytes. So we expected that NeuPSA would be very rare as well."

Instead, Dr. Moe and his colleagues discovered that this previously unknown molecule was expressed in every single type of human tissue they tested, spanning all the major organs. Not only that, but Dr. Moe also found NeuPSA in much higher amounts in tumors compared to normal tissues and in cancer cell lines. Examples included human melanoma, T cell leukemia, and two neuroblastoma cell lines. While this ruled out the possibility of using NeuPSA as a vaccine target against bacterial infections for infants and children, it opens up a whole new area of research in the treatment of cancers.

“Now that we know NeuPSA exists in all these different cells, both healthy cells and cancerous cells, the question becomes: ‘What is it doing?’.”

“Now that we know NeuPSA exists in all these different cells, both healthy cells and cancerous cells, the question becomes: ‘What is it doing?’,” says Dr. Moe.

The complete answer to that question will probably not be known for some time, but at a minimum, Dr. Moe’s studies suggest that NeuPSA may be an incredibly useful target for the development of new methods of treating cancer. In particular, the most dramatic results of the studies were that the Moe lab was able to demonstrate that antibodies directed against NeuPSA caused programmed cell death in all of the cancer lines they tested.

In addition, recent unpublished experiments from Dr. Moe’s lab suggest that NeuPSA could be a critical player in cell adhesion and motility – how cells stick to other cells and how they move around.

"We know that adhesion and motility are very important in cancer," Dr. Moe says. "The reason people usually die from cancer or have severe disease is because the cancer metastasizes. If the cancer stayed just as a localized tumor, it could be surgically removed, but that fact that the cancer moves to other parts of the body, that is what the central problem is."

While the larger questions regarding the function of NeuPSA still need to be explored, the Moe lab is already working on ways to use NeuPSA as a potential target in cancer-fighting vaccines and drugs, both in the ongoing development of a vaccine to elicit the same anti-cancer antibodies they used in their studies, as well as in the development of designer molecules to inhibit NeuPSA in cancer cells. While a novel treatment available to patients is far in the future, Dr. Moe's latest research provides a glimmer of hope for turning a new corner in current cancer treatment approaches.

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Thursday, January 12, 2012 12:50 PM

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