A new approach is being looked at in the way of fighting cancer cells.  One of the major problems facing us in the fight against cancer is the fact that our own immune system lacks the capability to recognize tumor cells as a foreign invader.  This leads to the problem of cancer cells being able to grow and metastasize throughout the body without causing an immune response.  One of recognizable traits to many of these cancerous cells is the glycosylation, cell surface carbohydrates (see fig 1), of the cell.  There is a noticeable difference in this glycosylation of cancer cells and normal cells.  It is this difference that now may be the new target of science in the fight against cancer.  The difference in these cancerous cells is their expression in some instances of antigens that are not found in any tissue that is normal.  Besides these novel antigens there is also an over expression that is found on most metastasizing tumor cells.  The new approach that is being developed to target this over expression of antigens is to make non natural antigens that won't be recognized by the body as self, and thus spurring an immune response.
 
 

    An example of over expression of these carbohydrates on the cell surface of cancer cells is the abundance of sialic acids on metastic cancer cells.  This is a very helpful observation for beginning the cell surface transformation that may lead to immune response by the body.  We already know of the biosynthetic pathway (see fig 2) that places these sialic acids on the cells surface, and from there can begin the research of exactly how to place novel non-natural sialosides on the cells surface.

    Making non natural sialosides to be place onto the cells surface isn't the only thing that must be considered when deciding exactly how to structure these carbohydrates.  We must also be able to transfer these non natural sialosides to the cells surface.  We have found this to be a very tricky obstacle to overcome.  To do this we have studied the biosynthetic pathway of sialic acid in order to determine which sialosides are actually probable moieties to place on the surface.  To do this the non natural precursors to sialic acid must be able to be taken up by the cell, and incorporated onto the cell.  This has proven to be much harder than previously thought due to the specificity of this pathway (see above).  Through previous research that has been done on this biosynthetic pathway we have found the enzymes of this pathway to be much more specific than believed, and thus much harder to incorporate novel sialosides onto the cells surface.  The most amount of research on the specific enzymes has been done on the ManNAc-6-kinase which is the first enzyme of the pathway.  This enzyme has been shown to be very sensitive to changes in the side chain at C2 to more than 5 carbons.

    Another way that non natural sialosides act in the glycosylation process is as chain terminators for PSA (polysialic acid).  These chains are found in the normal adult brain, and on tumors. It is not found on normal cells of the body, and that is why it is perfect for study with these non natural sialosides.  With the termination of these chains it is that metastic potential of the cells will be decreased (see fig 3).
 
 

    A final look that I'll take at new theoretical cancer fighting approaches targets mucins on the outside of cells.  These mucins are found to be over expressed on many metastic cells.  Mucins are O-linked glycoproteins that are found on cell surfaces like many of the other carbohydrates that I have discussed (see fig 4).

    It is thought that the denseness of the mucins on the outside of cells contribute to the metastasis potential of cancer cells due to steric hindrance causing loss of cell to matrix and cell to cell interactions.  It is thought that if the denseness of the mucins could be controlled to suppress this O-linked glycosylation and therefore reduce the potential for metastasis of cancer cells.  This approach gives two enzymes that may be targeted.  The first enzyme is UDP-GlcNAc/GalNAc-4-epimerase.  This enzyme creates a substrate for use by UDP-GalNAc peptidyltransferase which is the enzyme that installs the first GalNAc residues on the mucin.  If an inhibitor were found for either of these enzymes we could severly limit the amount of mucins that were able to be produced on the cells surface and by doing this decrease metastic potential of cancerous cells.

    All of these new theoretical approaches to inhibiting and destroying cancer, and metastasis hold much promise.  I believe that it is through the learning of the cell to cell interactions using these glycosides that we will be making our next breakthroughs in the fight against cancer, and one step closer to a cure.