Pancreatic cancer strikes less than 2% of the population, yet this brutal disease has one of the highest mortality rates among patients, with a mean survival time of only four to six months after diagnosis. Scientists hope that early detection will be the key to increasing patient survival rates, and Dr. Kimberly Kelly from the University of Virginia has dedicated her research to learning more this deadly cancer. Within the year her team hopes to go to clinical trials with new biomarkers to target early indicators of the cancer, as well as stem cells left over after removal.
Kelly's strategy begins with bacteriophages: viruses that bind to bacteria and cause them to create millions of copies of the virus phage. In a technique developed some years ago, scientists attach a random amino acid sequence to the bacteriophage which causes the host bacteria to also generate millions of random peptides. Kelly and her team take this zoo of peptides and throw them up against pancreatic cancerous cells and see what sticks. Peptides that "stick" to the cancer cells are chemically bound to proteins on the cell surface and become new biomarkers for those cells. This technique can be used for any cancer or disease and requires very few lab resources, as the peptides can all compete for the cancer cells at the same time so they don't need individual handling or individual tissue samples. It's also very fast. The trade off, says Kelly, is that it may not find all of the cell surface proteins, but it will find the high expressers. They've identified about thirty where there could be tens of thousands on the cell surface.
After finding a group of desired peptides and producing them synthetically, the team worked to attach marker molecules to the peptides. Thus, they can inject the patient with the peptide, which will bond to the cancer cells, and the marker will appear in a scan of the patient. An iron oxide molecule will appear in an MR scan, and an indium molecule will appear in a SPECT scan. The team is looking for cancer cells as well as cancer stem cells and pre-cancer lesions. The lesions may help in early detection, while stem cells left behind after tumor removal are often what cause recurrence. This targeting of specific cells could provide information about what type of treatment doctors should pursue in individual patients or eventually assist in targeted drug delivery.
Their progress is approaching a critical phase as they hope to have the first human trials ready within a year. They are in the process of completing preclinical trials and toxicology tests. The first steps will be small; simply making sure the biomarkers work in humans, and then identifying pre-cancer lesions. Ultimately, she says, early detection and treatment is the goal.
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