Synthetic Biomarkers Could Reveal Tiny Ovarian Tumors

An advanced approach using synthetic biomarkers to detect ovarian cancers has been developed by MIT researchers. The approach was tested in mice and has detected tumor nodules which are smaller than 2 millimeters in diameter. In humans it could detect tumors for 5 months earlier than what is feasible with currently available blood tests.

A synthetic biomarker is used for the new test. This biomarker is a nanoparticle which can interact with tumor proteins to liberate fragments. These fragments can be identified in a urine sample of the patient. This way of detection is clearer than the natural biomarkers which are found in fewer quantities on the patient's blood.

Sangeeta Bhatia, a member of MIT’s Koch Institute says that we engineered our biomarker 15 times better than earlier version and compared it with a blood biomarker in a mice model of ovarian cancer to demonstrate that we could do it.

Nanoparticles As Synthetic Biomarkers

Initially, Bhatia reported the approach of detecting cancer with synthetic biomarkers in 2012. This approach calculates the activity of endoproteases “ protein-cutting enzymes. These enzymes are produced by tumors to help employ blood vessels and attack the tissues surrounded in that location for growth and spread of cancer.

To identify this kind of enzyme, the researchers developed nanoparticles covered with peptides that can be cut by specific proteases called MMPs. When injected into a mouse, these nanoparticles inactively settle at the tumor site. MMPs slice the peptides to release smaller reporter fragments which will be filtered out by the kidney and collected in the urine. A simple paper-based test can be used to detect those reporter fragments from the urine.

For this study, researchers made use of two new approaches to amplify the sensitivity of their detector. The first approach was to modify the polymer's length that binds the peptides to the nanoparticle. This modification also reduces the slicing by the non-target enzyme.

As a second approach, the researches included a targeting molecule called tumor-penetrating peptide to the nanoparticles. This addition makes the nanoparticles to collect at the tumor site in higher numbers and leads to amplify the number of cleaved peptides that concentrates in the urine.

With the help of these two enhancements, the researchers boosted the sensitivity of the sensor by 15 times, which they later found to be adequate in diagnosing ovarian cancer that consisted of tiny tumors (2 millimeters in diameter) in mice models. The researchers also tested this strategy in the liver where they were capable of detecting tumors that occurred in the colon. In human beings, colon cancer frequently spreads to the liver and creates small tumors that are hard to detect; the same applies in ovarian tumors.

Better Diagnosis

As of now, physicians depend on blood biomarkers made by ovarian tumors; however these markers do not collect in adequate concentrations to be detected until the tumors grow big as 1 centimeter in diameter. These blood markers can be detected only after 8 to 10 years after their formation. With the other available diagnostic tool, ultrasound imaging, tumors which are 1 centimeter or larger can be detected.

This new approach can detect tumor five months prior to the currently available diagnostic methods. This might create a major impact for some patients.

Written by Lax Mariappan, Msc

Image Credit: Nephron/CC BY-SA 3.0 – MIT