New Ovarian Cancer Screening Method Could Detect Tumors Earlier

When discovered during its early stages, ovarian cancer can be treated. Unfortunately, it is usually found only after it has progressed to more advanced stages. Improved screening techniques are the key to increasing the survival rates of ovarian cancer patients.

Engineers at MIT have finally developed an improved method for uncovering ovarian tumors earlier during the progression of ovarian cancer than ever before. During testing, the researchers were able to find ovarian tumors smaller than 2 millimeters in diameter, which could mean than doctors may one day be able to detect ovarian tumors in humans at least five months sooner than they can with the current blood test methods ("New Technology Can Detect Tiny Ovarian Tumors," 2017).

Ovarian cancer is almost always discovered during its late stages. In fact, more than 70 percent of women who are diagnosed with ovarian cancer are not diagnosed until they have progressed to the later stages: stage III or stage IV. It is during these later stages that ovarian cancer is the most difficult to treat and has the highest rate of fatality among those it attacks. If, however, ovarian cancer could be detected at its earliest stage, stage 1, the survival rate could be around 93 percent. Detection at stage 2 leaves a little lower survival rate but still gives the patient better odds than if the ovarian cancer goes undetected until the later stages.

To date, the most current methods for screening women for ovarian cancer have been limited and widely unreliable. The most recent methods for screening women for ovarian cancer include a pelvic exam, a transvaginal ultrasound, and a blood test that measures the blood levels of the protein CA-125. Although these methods can be helpful in detecting ovarian cancer, none of them are deemed effective at detecting ovarian cancer during stage I, when it is easiest to treat (Morris & Gordon, 2010).

What does the new test entail?

A new test that uses a synthetic biomarker has recently been developed by researchers at MIT. A synthetic biomarker is a very tiny particle that interacts with the proteins of a tumor is such a way that it causes fragments to be released into a patient's urine. This new urinalysis method seems to produce a much clearer signal than the protein biomarkers that have been found in a patient's bloodstream during later stages of ovarian cancer.

The team was able to create a sensor that was an estimated "15 times better than previous versions," according to Sangeeta Bhatia of MIT's Koch Institute for Integrative Cancer Research and Institute for Medical Engineering and Science and the senior author of the research study. Bhatia said that the team compared their method against a blood biomarker found in a mouse specimen with ovarian cancer and showed its improvement over the blood biomarker.

Bhatia first suggested that cancer could be detected with the use of a synthetic biomarker back in 2012. This new method can measure the activity of endoproteases, which are protein-cutting enzymes. Tumors creates endoproteases to help invade surrounding tissues through the recruitment of blood vessels. It is in this method that cancer is able to strengthen, grow, and metastasize (or spread to other areas of the body).

In order to detect these enzymes, the team of researchers had to design nanoparticles that were coated in small fragments of protein (called peptides). The peptide can then be "cleaved" by MMPs, a specific type of proteases. After this solution was injected into a mouse specimen, the particles would pool near the site of the tumor. In order to liberate the tiny reporter fragments, the MMPs cleaved the peptides. The reporter fragments are then filtered out by the kidney and detected in concentrations in the urine using various different detection methods. One of the simplest detection methods was a basic paper-based test.

In 2015, the team of MIT researchers needed to gain a greater understanding of several of the factors concerning the system. They gained this understanding using a mathematical model that they created and then published in a paper. Three of the many factors that they needed to know was how efficiently the particles encounter protease, how they circulate throughout the body, and at what rate did the protease cleave the peptides. Through the use of this customized mathematical model, the researchers were able to discover that they would have to improve the sensitivity of the system by at least one order of magnitude in order to detect tumors that were no larger than 5 millimeters.

In this most recent research study, the team of researchers have discovered two brand new and improved methods that can boost their detector's sensitivity to the level that the test requires. The first of the two strategies is to stretch the length of the polymer that is used to tether the nanoparticle to the peptides. It has been found that when the polymer is optimized to a specific length that the peptides are cleaved by the proteases at a much higher rate. This new polymer optimization method also helps to decrease the number of nontarget enzymes that are cleaved.

The second method that was adjusted by the team of researchers is the addition of a targeting molecule that is known to be a peptide that penetrates tumors. This targeting molecule is added to the nanoparticles and then causes the nanoparticles to accumulate in the area around the tumor in a much higher concentration. This much higher concentration of nanoparticles at the tumor site causes an increase in the amount of cleaved peptides that are secreted and that can then be detected by a test of the urine, resulting in a more definitive and earlier detection of an ovarian cancer tumor.

Could this be helpful for other cancers?

When the team of researchers combined these two improved modifications to their detector, they found that they were capable of enhancing the detector's sensitivity by 15 times, which they proved was sensitive enough to detect ovarian cancer tumors as small as 2 millimeters in diameter in their mice specimen. Similar to ovarian cancer tumors, colon cancer that spreads to the liver often forms tiny tumors that are difficult to detect. In addition to detecting ovarian cancer tumors, the team of researchers were also able to detect tumors in the liver that had originated from the colon, which could mean that the screening method could also be used to detect colon cancer tumors. If this new screening method can be used to detect both ovarian and colorectal tumors, then it may be able to be adapted to detect other cancer tumors as well.

Ovarian cancer is a very difficult disease to beat during its later stages. If discovered early on, the chance for survival goes up. The best weapon for battling ovarian cancer, as with any type of cancer, is early detection. Early detection could mean the difference between life and death for many women each year. Every time a new screening method is detected, more lives are saved.

References

Morris, J.L. & Gordon, O.K. (2010). Positive Results: Making the Best Decisions When You’re at High Risk for Breast or Ovarian Cancer. Prometheus Books. Amherst, New York.

"New Technology Can Detect Tiny Ovarian Tumors" (2017). [Web]. In Science Daily. Retrieved from: https://www.sciencedaily.com/releases/2017/04/170410123940.htm