Slovak chemist wants to help men avoid painful procedures

Ján Tkáč was awarded the ESET Science Award in 2019.

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Prostate cancer is one of the most common causes of death in men. Although tests exist to diagnose this disease, they are flawed and can produce misleading results, including false positives and false negatives.

That is why Slovak chemist Ján Tkáč and his team at the Institute of Chemistry of the Slovak Academy of Sciences are developing a completely new type of test. It may help you avoid painful procedures when you don’t need them.

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For several years, you have been working on developing an entirely new type of prostate cancer test based on nanotechnology. How is it different from what is commonly used in clinical practice today?

The uniqueness of our diagnostic test lies in the determination of glycan structures [complex sugars – Ed.]Tests that measure DNA, RNA, or various protein biomarkers are currently used to diagnose prostate cancer. Compared with biomarkers, changes in glycan structure better reflect cancerous changes in cells. For example, levels of PSA (prostate-specific antigen) in the blood can increase as a result of inflammation or after strenuous cycling.

On the other hand, a genetic predisposition does not necessarily lead to the development of the disease. Moreover, many DNA, RNA, or protein biomarkers can only be determined in post-biopsy tissue and cannot be used for early diagnosis. Changes in glycan structure can be measured in blood. Therefore, our test is minimally invasive and can be used to diagnose early stages of prostate cancer.

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How has nanotechnology helped your research?

Nanotechnology has helped design tests to fit into clinical practice. This is very important as standard methods of glycan measurement rely on expensive, space-consuming instruments and complex and lengthy assays. Our approach is based on cell phone-sized plates to measure the degree of color change in the sample. Color intensity is proportional to changes in glycans and, in a sense, to the stage of disease.

Should standard tests be replaced?

The current standard is the PSA test. However, it has a low accuracy of about 68% and is unreliable. So when it is difficult for urologists to determine whether increased values ​​are due to inflammation, benign disease, physiological enlargement of the prostate or cancer, the analysis can fall into a so-called gray zone. An uncomfortable situation. For both urologists and patients.

Many experts suggest that the PSA test is not at all suitable for screening for prostate cancer and should instead be used to monitor disease progression and the course of treatment. This is why international guidelines regarding the frequency of analysis, the appropriate age distribution of men to be tested, and safe values ​​have changed significantly over the past two decades.

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Are there more problems with the PSA test?

Tests can also give false-positive results, proving that the biopsy is negative. or false-negative results, allowing disease to develop. Neither type of result is desirable, so more reliable tests are systematically developed.

what are they?

one of them is PHI [prostate health index – Ed.] A test used in many countries. Accuracy is 73%, well below what urologists and patients expect. Currently, several methods, including ours, have been developed, with accuracies of about 84-86%. Our startup, Glycanostics, aims to increase the confidence level to about 90% by analyzing several types of glycans.

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A biopsy is used to confirm or rule out the presence of cancer. Does that mean this is no longer necessary?

A biopsy is still required to definitively confirm the disease and determine the stage. However, it is a very uncomfortable procedure that many men would like to avoid. A biopsy can cause complications such as inflammation of the prostate. However, biopsies are not completely reliable. This is because it can be difficult to obtain tissue from cancer-affected areas of the prostate.

That is why a biopsy is combined with magnetic resonance imaging (MRI). MRI shows problem areas of the prostate and allows targeted biopsies. It should be recognized that the prostate is a relatively small organ and the number of biopsies that can be performed is limited. Therefore, making the right decision is very important.

Why design tests based on nanotechnology What are the advantages?

Nanotechnology enables faster analysis times and increased sensitivity. Thus, it offers the possibility of identifying small changes in glycan structure. This enables early diagnosis of cancer and the accurate analysis of large numbers of samples in a short time. Also, very small samples are sufficient. At the same time, our technology can be easily transferred to the automated diagnostic equipment of major cancer laboratories.

What are the biggest benefits of testing?

This test helps urologists decide if a biopsy is necessary or if preventive testing with a blood analysis is sufficient.At the same time, clinical validation [i.e. testing to meet clinical standards – Ed.] Our test shows that it can be used to distinguish between early-stage and late-stage prostate cancer patients. In the former, the early stages are not life-threatening and can last for years, so active monitoring of the patient is sufficient. The latter requires surgery or treatment. Validation also revealed that our test could be used to monitor treatment success.

How does the test work and what does it look like?

First, a blood sample must be taken, primarily to remove cells such as white blood cells and red blood cells to prepare serum. This is also standard procedure for normal testing. One drop of serum is then mixed with the modified magnetic nanoparticles. Changes in glycan structure are then measured to derive specific values ​​that determine a patient’s probability of prostate cancer.

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Can your test be used for other types of cancer? Do you need to change anything to allow this?

Yes, I can. A small clinical validation of 100 samples showed that it can be used to diagnose breast cancer with a high confidence of 90%. This is very important because breast cancer is the most common cancer in women and has a higher mortality rate compared to prostate cancer. In this case, we measure changes in other types of glycans, but the procedure is the same. To confirm its high reliability, we are preparing clinical validation using hundreds of serum samples.

We also plan to validate the diagnosis of pancreatic and lung cancer in the near future. We are in contact with several clinical institutions in Slovakia and abroad to obtain high-quality serum samples for validation. Together, these contacts allow us to discuss the clinical practice requirements our test is supposed to address.

When will the test be available?

Our primary goal is to license our technology to large pharmaceutical or diagnostic companies that sell the tests themselves. We believe it will be possible in a year or two. However, we are also considering another method. That means writing and distributing the tests yourself. If so, it will be available in Slovakia and some countries within a year.

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What are the symptoms of prostate cancer? What should a man look for?

Prostate cancer is one of the most common causes of death in men. The main reason is delayed diagnosis. [when the cancer is] in the aggressive stage. Prostate cancer can go unnoticed and progress for a long time without any obvious symptoms. One of the symptoms is problem urination. However, this does not automatically imply cancer and may be related to physiological enlargement of the organ with aging.

Problematic urination should be the first red flag for a man and a sign of a visit to a urologist. Get a preventative checkup. This is the best way to detect the disease in its early, non-life-threatening stages.

You have received several prestigious grants. How important were these to your research?

The first ERC start-up grant was very important to the development of my scientific group. The group focuses primarily on basic research and the potential of nanotechnology and nanomaterials in the field of glycomics. [a scientific discipline devoted to the study of the roles of glycans in our body – Ed.]The key to this phase was Tomáš Bertók. He introduced the group to many techniques he used in solving the project. The results of basic research were implemented in applied research. Applied research used his second ERC proof-of-concept grant and focused on optimizing cancer diagnostics.

The SME Instrument 1 Grant made it possible to realize a commercial application of the test and a feasibility study was carried out. The arrival of her CEO Eva Kováčová, who has many years of experience in pharmaceutical companies, has greatly improved the quality of the team. This allowed her to receive her first venture capital investment and her EIC accelerator grant as one of her 68 companies across the EU. Without them, our company would not have been able to develop successfully.

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What is the situation for budding scientists in Slovakia in this regard? Could they receive a grant?

The situation is very complicated because funding agencies do not have enough money to fund all quality projects. It is very difficult for young scientists to compete with experienced scientists. Ideally, we should take concrete steps to help young people. A little light at the end of the tunnel is an initiative for universities, SAVs, or their institutions to support promising young scientists from internal sources.

However, this is not a systematic solution, which is why very often bright young scientists leave Slovakia after completing their Ph.D. Very few will come back. For such a small country this makes Slovakia very poor. Our priority is to invest in top science that has the potential to lead to value-added solutions in the future. For this purpose, financial sources from structural funds should be used more effectively.

This article is supported by the ESET Foundation. ESET Science Award To be an excellent scientist every year. Slovak chemist wants to help men avoid painful procedures

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