Survival rates for ovarian cancer can be significantly increased if it is detected at an earlier stage. Now, MIT researchers have developed a far more sensitive way to reveal ovarian tumors. In tests in mice, they were able to detect tumors composed of nodules smaller than 2 millimeters in diameter. In humans, that could translate to tumor detection about five months earlier than is possible with existing blood tests.
The new test makes use of a "synthetic biomarker" - a nanoparticle that interacts with tumor proteins to release fragments that can be detected in a patient's urine sample. This kind of test can generate a much clearer signal than natural biomarkers found in very small quantities in the patient's bloodstream. The approach could also be adapted to other cancers, according to the research published in Nature Biomedical Engineering.
The strategy of using synthetic biomarkers to diagnose cancer was first reported in 2012. The method
measures the activity of protein-cutting enzymes called endoproteases, which are made by tumors to help recruit blood vessels and invade surrounding tissues so the cancer can grow and spread.
To detect this sort of enzyme, the researchers designed nanoparticles coated with small protein fragments called peptides that can be cleaved by particular proteases called MMPs. After being injected into a mouse, these particles passively collect at the tumor site. MMPs cleave the peptides to liberate tiny reporter fragments, which are then filtered out by the kidney and concentrated in the urine, where they can be detected using various methods, including a simple paper-based test.
Currently, doctors can look for blood biomarkers produced by ovarian tumors, but these markers don't accumulate in great enough concentrations to be detected until the tumors are about 1 centimeter in diameter, about eight to 10 years after they form. Another diagnostic tool, ultrasound imaging, is also limited to ovarian tumors that are 1 centimeter in diameter or larger. Being able to detect a tumor five months earlier, which the MIT researchers believe their new technique could do, could make a significant difference for some patients.
In this paper, the researchers also showed that they could detect disease proteases in microarrays of many tumor cells taken from different cancer patients. This strategy could eventually help the researchers to determine which peptides to use for different types of cancer, and even for individual patients.
"Every patient's tumor is different, and not every tumor will be amenable to targeting with the same molecule," the researchers said. "This is a tool that will help us to exploit the modularity of the technology and personalize formulations."
The researchers are now further investigating the possibility of using this approach on other cancers, including prostate cancer, where it could be used to distinguish more aggressive tumors from those that grow much more slowly.