‘Smart' Molecules Devised for Breast, Ovarian Cancer Therapies

New non-toxic and targeted therapies for metastatic breast and ovarian cancers may now be possible because researchers have found that a protein called podocalyxin, which had previously been shown to be a predictor of metastatic breast cancer, changes the shape and adhesive quality of tumor cells, affecting their ability to grow and metastasize.

In a collaboration between stem cell and cancer scientists from the University of British Columbia (UBC; Vancouver, Canada), their discovery demonstrated that the protein not only predicted the spread of breast cancer cells, it likely helped to cause it. The study's results were published online in March 2007 by the Public Library of Science.

"We believe we've found a new important culprit in metastatic breast cancer, which opens up an entirely new avenue of cancer research,” stated Dr. Calvin Roskelley, an associate professor of cellular and physiological science who specializes in breast cancer and is co-senior principal investigator. "The culprit is hiding in plain sight on the surface of tumor cells, so we are now developing ‘smart' molecules to block its function. The ultimate goal is to generate new targeted, non-toxic treatments--very different from the standard ‘slash and burn' chemotherapy.”

The researchers found that podocalyxin considerably expands the non-adhesive face of cells, allowing individual cells to push aside adhesion molecules located between tumor cells. The "freed” cells then move away from the original site to form new tumors at other sites. Furthermore, the protein causes tumor cells to grow microvilli, or hair-like projections, that may help propel cancer cells to other sites.

Moreover, when the protein expands the non-adhesive face of cells, it pulls along with it a second protein called NHERF-1--a protein previously shown to be implicated in cell growth and invasion. The researchers now believe the process applies to difficult-to-treat invasive breast and ovarian tumors.

"We're now tapping into what causes the characteristic cell shape changes seen in cancerous tumors and possibly how these cells grow and metastasize. It gives us a whole new target for therapy,” said associate professor of medical genetics and stem cell expert Dr. Kelly McNagny, co-senior principal investigator. "If we can block the protein, we may be able to stop the spread of cells.”

The next steps of the research will involve advancing the research in animal models, designing antibodies to block the function of the protein, and working with the UBC-based Center for Drug Research and Development to identify new therapies to combat metastasizing cancer.

According to the researchers, data gleaned from this discovery may speed development of new therapies to within 10 years.


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