By taking two standard laboratory techniques - capillary electrophoresis and antibody-based protein detection - and shrinking them to the nanoscale, researchers at the Stanford University School of Medicine have created a new method for detecting miniscule changes in the levels of proteins associated with cancer.
In a study published in the journal Nature Medicine, the investigators used their new device to analyze whether individual cancer-associated proteins were present in the tiny samples and even whether modifications of the proteins varied in response to cancer treatments. Although the study focuses on blood cancers, the hope is that the technique also might provide a faster, less invasive way to track solid tumors.
"Currently, we don't know what's going on in a patient's tumor cells when a treatment is given," said Alice C. Fan, M.D., who along with Dean W. Felsher, M.D., headed the team that developed this nanofluidic proteomic immunoassay (NIA) system. "The standard way we measure whether a treatment is working is to wait several weeks to see if the tumor mass shrinks. It would be a leap forward if we could detect what is happening at a cellular level."
Dr. Felsher, who is a member of the Center for Cancer Nanotechnology Excellence Focused on Therapy Response based at Stanford University, added, "This technology allows us to analyze cancer-associated proteins on a very small scale. "Not only can we detect picogram levels - one-trillionth of a gram - of protein, but we also can see very subtle changes in the ways the protein is modified."
Variations in the way a protein is modified, or phosphorylated, can affect how it functions in tumor progression. Cancer cells often evade common therapies by altering levels of protein expression and degrees of phosphorylation. Analyzing repeated small samples from a tumor undergoing treatment may let doctors head off rogue cells before they proliferate into a more resistant tumor as well as identify patients likely to fail standard approaches to treatment.
Drs. Fan and Felsher collaborated with researchers from Cell Biosciences, Inc., to create the NIA system that separates cancer-associated proteins in narrow capillary tubes based on their charge, which varies according to modifications on the surfaces of the proteins. Two versions of the same protein - one phosphorylated and one not - can be easily distinguished because they travel different distances in the tube. The researchers then use antibodies to identify the relative amounts and positions of the various proteins.