UVA Study May Lead to New Treatments for Melanoma, Ovarian Cancer

Most of us may not realize it, but our cells have their own early warning and defence mechanisms against cancer. Understanding how these mechanisms operate and how they may be used to thwart cancer from developing or spreading has been the focus of Dr. Angela Zarling and her research team at the University of Virginia Health System.

The latest study completed by Dr. Zarling and her colleagues used melanoma and ovarian cancer cells to track the chain of molecular activity through which our bodies identify and respond to invasive malignancies. The researchers are now extending their analysis to breast cancer, leukemia and lymphoma. Published this month in the Proceedings of the National Academy of Sciences (PNAS), the study confirms the link between the body's signalling activities and its ability to deploy protective cells - called cytotoxic T cells. The study also demonstrates the ability of these cells to selectively recognize and target tumours. Malignancies associated with cancer often result when aberrant signalling pathways within the body stimulate unchecked cell growth, protect cells from death and allow transformed cells to metastasize to other areas. The phosphopeptides studied by Dr. Zarling and her team are strongly linked to these pathways and considered capable of generating cytotoxic T cells that clear tumours effectively. According to Dr. Zarling, study findings offer insight to the signalling pathways that occur within the cancer cell and provide a marker that identifies that cell as transformed. Because several peptides identified in the study are shared by other cancers, they could be utilized for vaccines against those malignancies as well. Working with Dr. Craig Slingluff of the UVA Human Immunotherapy Centre (HITC), two of Dr. Zarling's collaborators - Dr. Victor H. Engelhard and Dr. Donald F. Hunt - have successfully developed peptide-based vaccines for melanoma. Over the next several years, these investigators, in collaboration with the HITC, will evaluate the utility of these phosphopeptides for tumour control and as a cancer vaccine. If successful, they could become the next generation of peptide-based immunotherapy, yielding stronger immune responses that enable destruction of tumours with less collateral damage to normal tissue. (Source: University of Virginia: October 2006.)