It took only a few stray cancer cells to direct Dr. Amanda Paulovich's research path.
While training in both clinical medicine and basic science, she treated oncology patients who appeared cured after treatment, but the best of scans couldn't detect a small number of cells that sometimes escaped the original cancer site. Those renegade cells went on to become hard-to-stop metastatic cancer.
"The reality of how difficult it is to treat a tumor once even a few cells have escaped the primary site was quite overwhelming," she said. "It made me realize how so few cells could make our treatments largely ineffective."
The quest for Paulovich became — and remains — to find miniscule molecules in the body in order to diagnose and eliminate cancer long before it becomes a tumor or errant cells.
This promising field of biomarker discovery is in its infancy. The challenge and potential of such work led Paulovich to Fred Hutch in 2004 to direct its early detection research.
Genes instruct cells, and proteins do the work that drives both cellular health and disease. Genomics is the study of gene sequences; proteomics analyzes proteins.
So while genes hint at the likelihood of developing a certain disease, proteins show what is currently happening in a patient. The discovery that proteins are leaked by tumors into the blood and urine could lead to better diagnostic tools for cancer detection.
Thousands of potential biomarkers have been discovered, and this list continues to grow. But the sobering reality is that very few of these candidates have been validated, and even fewer have reached patients.
Paulovich's lab is developing technologies to rapidly screen large numbers of candidate protein biomarkers in the hundreds of patient samples necessary for verification. Identifying these key biomarkers has disease implications far beyond cancer.
Paulovich and her colleagues recently took a big step forward in overcoming limiting factors validating biomarkers for clinical use: a lack of standardized technologies and methodologies.
A national scientific network that includes Paulovich's team may have solved that dilemma by creating a new method for detecting and quantifying protein biomarkers in body fluids.
This novel approach holds the promise of ensuring that only the strongest biomarker candidates will advance down the development pipeline.
"If the technologies meet their potential, we'll stop treating patients based on population averages," Paulovich said. "The idea behind personalized medicine is figuring out what's the ideal intervention for you, which will cut costs and improve our treatments — that's the ultimate goal. If we can make it work, it will have a giant impact."
There are already examples of this approach in lung and breast cancer treatments. "It's just a matter of making what are now the exceptions, the rule," she said. "I think we're only a decade or two away."