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Aggressive Prostate Cancer Test Targeted by UK Researchers for Early Detection

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NEW YORK (360Dx) – A team of researchers at the University of Birmingham in the UK was recently awarded £275,000 ($326,000) to develop a new test for the early detection of aggressive prostate cancer.

The team, led by Paula Mendes, a professor of nanoengineering and surface chemistry at the university, received the grant through Prostate Cancer UK's Research Innovation Awards program. The researchers aim to develop a new assay that they believe will be more accurate than conventional tests that measure the amount of prostate specific antigen (PSA) in a patient's blood.

According to Prostate Cancer UK, about 11,500 men die of prostate cancer in the UK each year. It's the most common cancer in men in the country.

"If your PSA level is more than 4 nanograms per milliliter, you might have prostate cancer," noted Mendes. "But there is a 50 percent false positive rate, and men who are positive still have to go to biopsy," she said. "You also cannot detect prostate cancer at an early stage because men with low PSA levels can still have prostate cancer," she said. About a quarter of false negatives are missed at the early stage of the disease.

Mendes' solution to this problem is to draw on her experience in nanoengineering to develop a chip that is capable of detecting not only prostate cancer at an early stage, but to determine how aggressive the disease is so that appropriate treatment decisions can be made.

The approach is based on using colored nanoparticles that bind to certain sugars attached to PSA proteins, called glycoproteins. According to Mendes, not only are these glycoproteins indicative of disease, but they also serve as markers for its aggressiveness.

"It is clear now that there are some sugars related to aggressive prostate cancer," said Mendes. "We know what glycans we need to detect. This is where we come along with our technology."

Birmingham's technology is based on combining the glycan with certain receptors, and then fixing it on a surface where the receptors are in a position to detect those glycans and not others. The research team discussed the approach in a 2015 paper in Chemical Science.

The paper described in detail the group's detection platform, self-assembled monolayer (SAM) made of polycrystalline gold deposited on glass. Protein complexes targeting glycoproteins were manufactured on the prepared surfaces, and following interaction with samples, binding was detected by surface plasmon resonance using a Reichert SR7000DC Dual Channel Spectrometer.

Mendes said the group has been developing the technology since 2013 and that other papers are forthcoming. The researchers believe their approach could overcome the drawbacks of using antibodies for detecting glycoproteins in various tests, such as their lack of specificity, as they are unable to distinguish different glycosylated proteins.

"The idea is that, so far, glycans have not been detected well," Mendes noted. "For the first time, we had a platform where we could place the receptors in the right place to detect the right glycans," she said. "Now we have developed the technology and we have selectivity for the PSA but there is still some background there."

Indeed, one of the core goals for Mendes' group is to move its current assay to an enzyme-linked immunosorbant assay (ELISA) format, which would permit greater clinical uptake. "We have this technology on a gold chip but it will never go to the clinic," said Mendes. "We need something that will be easily implemented in the clinic, and this will be an ELISA."

To accomplish that, Mendes and fellow investigators will need to make the assay work with nanoparticles that fluoresce. Blood samples will be immobilized on ELISA plates, and the nanoparticles will detect the glycans that are associated with aggressive prostate cancer.

This will benefit not only men who have aggressive forms of the disease, enabling them access to better treatment at an earlier stage, Mendes noted, but also men who have so-called indolent prostate cancer, where the cancer never presents with any symptoms or spreads, and who have in the past typically been assigned surgery without any need to have it performed.

Birmingham's current Prostate Cancer UK grant is set to run for the next two years.  Mendes said her group will work with University College London to source samples to develop its test, both from men with aggressive and indolent forms of prostate cancer, as well as various PSA levels.

Commercialization of an assay is certainly a goal, and Mendes said that the university has commissioned a business report, along with guidance from consultants outside the university to advise on a possible path to market.

"As soon as we are ready, we will engage with industry and license [the technology] so they can quickly bring it to market," she said. Mendes noted that the current two-year project is a "proof of concept" for the new assay, and to validate the resulting test will require about 1,000 samples in the future.

The resulting test would be positioned as an early-stage prostate cancer test for the clinical market. Should it reach the market, it will join a growing number of tests that have been designed to overcome the same shortcomings with conventional approaches. MDxHealth, for instance, sells SelectMDx, a urine-based assay that is intended to help stratify patients who have clinical signs of a possible prostate cancer into those at higher and lower risk.

"Early detection is key because you open up the number of options of treatment you can have," Mendes said. "We are able with this technology to not miss the 25 percent missed by the current PSA test," she said. "It is in that sense we will make a difference. This is where we want to be — early and accurate."