Newspaper “Zinātnes Vēstnesis”, No. 5 (664), May 25, 2026 Author: ILZE KUZMINA
On the day I interview Professor Aija Linē, she is still the Scientific Director of the Biomedical Research and Study Centre (BMC) and leads the cancer biomarker research group at the center. Starting in June, this work will continue at the National Research and Innovation Institute, which merges BMC with the Institute of Organic Synthesis. In this conversation, I ask how research will progress in the merged institute, as well as what has already been discovered in oncology diagnostics.
Together with your colleagues, you have been working for a long time looking for methods for earlier tumor diagnosis. What are the achievements, and how has the ability to diagnose tumors early improved over the last, say, 10 years?
I would say that noticeable progress has been made relatively recently. For now, however, these developed biomarker tests, with a few exceptions, are not yet widely available and used in clinical practice. But I think that in the relatively near future, at least some of the newly developed tests will reach patients. This is not just about Latvia; globally, blood tests for cancer diagnostics are not yet widely used either.
The so-called liquid biopsy methods are closer to practical application. They make it possible to monitor how the tumor’s mutational profile changes in the blood. This means that cell-free DNA is detected in a blood sample, fragments of which have originated from tumor cells and contain tumor cell mutations. By measuring the quantity of these mutations, it is possible to determine whether the disease is returning or not in a patient who has had a tumor surgically removed. This provides an opportunity to detect relapses in a timely manner, as well as to conclude whether new mutations have arisen in the cancer cells present in the body.
Any analysis in which cancer cells or molecules derived from them are detected in bodily fluids is called a liquid biopsy. Most often it is blood, but it can also be urine, saliva, breast milk samples, or similar. So, in this case, a tissue biopsy is not taken from the tumor, but cancer cell molecules are detected in a fluid sample. Such tests are already commercially available, meaning they are entering clinical practice.
Liquid biopsies have several applications, but they have advanced the most in monitoring the effectiveness of anti-cancer therapy. Thus, for patients already diagnosed with a tumor, the liquid biopsy method can be used to monitor changes in the tumor or to diagnose a relapse early. A second application could be early diagnosis, but using this method for that purpose would be more difficult, because in this case, we do not know specifically what we are looking for in the blood sample. If we know absolutely nothing about the specific patient’s tumor, then sequencing of all cell-free DNA could be performed. That way, one can attempt to detect changes that might indicate the presence of a tumor.
Speaking of early diagnosis, I know there are several blood tests currently being tested in clinical trials. However, as far as I know, they are not yet widely used.
Returning to liquid biopsy methods, you are also working on research in this field yourself. How is that progressing?
What we are studying are so-called extracellular vesicles. They are small: from 50 nanometers to one micrometer. They are vesicles enclosed by a cell membrane.
Such vesicles are secreted not only by cells of the human body, but actually by all life forms, including bacteria and fungi. Some of the vesicles secreted by cancer cells remain in the tumor tissue, while some enter the bloodstream. Vesicles present in a cancer patient’s body contain various molecules that originate from cancer cells. Therefore, we can find vesicles produced by cancer cells in a human blood sample, and by analyzing either their RNA (ribonucleic acid) or protein composition, we can draw conclusions about both the presence of the tumor and molecular changes within it. This idea is not entirely new, though. From the moment vesicles were discovered, they have been studied extensively.
Everyone has vesicles, but what is important is that some of the vesicles found in the blood of cancer patients have originated from the tumor tissue. Consequently, by taking blood samples and analyzing the vesicles, it is possible to diagnose a tumor or predict its progression. Quite a few groups, including us, have conducted various studies analyzing the RNA content in vesicles. We have managed to find a series of RNA molecules that could serve as biomarkers for breast cancer diagnostics. Most of the markers found so far have relatively high specificity but low sensitivity. This means that the marker is present in only a small fraction of patients, most often 10% to 20% of patients. Thus, a single marker might only be usable for a tenth of patients. One can, of course, try to combine them, putting many such markers together into a single test, but the more different markers you include in one test, the harder it is to validate such tests in the clinic. Therefore, with current technologies, it would be quite difficult to bring such tests into clinical practice. This is a conclusion we have reached after 10 years of research.
Other scientific groups working in this field have reached similar conclusions.
How many years then pass from a scientist’s discovery to using that discovery in cancer diagnosis and treatment?
Definitely more than 10 years. I would like to say that within the next few years, we will see at least the first molecular tests for cancer monitoring.
Would they be available elsewhere in the world, or in Latvia as well? And to what extent is it possible for Latvian medical institutions to use the latest medications and methods within the framework of existing funding?
Funding is, of course, a big problem, but there are also positive examples where it is possible to use what has been developed relatively recently. For instance, a couple of years ago, the Oncotype test became available in Latvia as well. It is used to analyze gene activity in tumor tissue for breast cancer patients who have undergone surgery in stage I or II. By determining whether the patient has a high risk of the disease returning, the test helps decide if that specific patient needs chemotherapy, which has many unpleasant side effects. If the risk is low, chemotherapy can be avoided. This test has been widely used globally for more than ten years. There was a time when it was not available in Latvia, but now it is.
A few years ago, you already discovered that physical activity helps fight breast cancer. Are there studies being conducted on the impact of an active lifestyle on other types of cancer as well?
Probably yes, but we haven’t had the opportunity to pursue this topic further ourselves. Currently, I am trying to submit subsequent projects on this topic to secure funding. Our goal is to gain a deeper understanding of the molecular and cellular processes that occur in the human body during physical exertion and to find out how these processes affect tumor behavior.
Our first study was successful: it involved breast cancer patients receiving neoadjuvant chemotherapy. This is chemotherapy given in courses over about half a year to shrink the tumor and make it operable. The patients involved in the study exercised regularly—two to three times a week—following specially designed, personalized training programs. First, we saw that for the patients who exercised, the effectiveness of the chemotherapy was higher than in the control group. Second, by analyzing the tumor tissue, we found that for the patients who exercised, the cellular composition and gene activity in the tumor tissue differed from the control group—those patients who did not change their daily habits during chemotherapy.
The training group had a significantly altered immune cell composition and immune cell activity. Our hypothesis regarding the interaction of physical activity with the tumor is that during each workout, immune cells capable of being activated and migrating enter the blood from various tissue reservoirs, such as the spleen or bone marrow. It had already been proven previously that within twenty minutes after starting a workout, for example, the proportion of NK cells in the blood can increase up to 10 times. Afterward, these cells can infiltrate the tumor and destroy cancer cells within it. Thus, during each workout, the amount of activated immune cells capable of fighting cancer increases slightly within the tumor.
This likely happens due to the interaction of various factors, as blood flow increases and the concentrations of various hormones, neurotransmitters, and cytokines rise in the blood. For example, interleukin-6 and adrenaline play a significant role. That is the hypothesis we would like to test and verify further. The benefit for patients would be that, based on these data, we could develop a more precise training program that would better stimulate exactly those processes that are favorable for tumor destruction.
Unfortunately, there is also not enough money to fund high-quality and necessary scientific projects. But shouldn’t projects related to health and the relatively large number of oncology patients be a priority?
Failing to secure funding is a fairly normal process. In the Latvian Council of Science, the competition is such that fewer than one in 10 projects receive funding. It is enough for a reviewer to find just one flaw to emphasize for the project not to be approved.
And, in my opinion, there is no ground to say that some projects are more of a priority than others. That is why it is an open competition where everyone starts with the same rules. However, it is also true that in any competition, there is a certain element of a game of chance, and luck plays its part as well.
Nevertheless, other studies continue, for example, in the field of the aforementioned extracellular vesicles. We are studying a conceptually new technology whose principle is based not on the molecular content of the vesicles, but rather on how they affect specially engineered biosensor cells. In the study, we take a blood sample from a patient or a healthy person, isolate the vesicles, add them to the biosensor cells, and see how gene activity changes. We expect that vesicles in the blood of cancer patients will affect processes that vesicles from a healthy person do not affect.
If this hypothesis is confirmed, fundamentally new types of liquid biopsy tests could eventually enter practice, based not on the detection of cancer cell molecules, but on their functions.
When was this study started, and how far have you come in this research?
This is a BioPhot platform project, where the principle is that each project lasts no longer than one year. Within this one year, we must be able to raise the technology readiness level by one stage. If we were at TRL 2 when applying for the project, then within one year we must reach the TRL 3 level. If we succeed, we will be able to apply for the next round with the hope of receiving funding for the next steps. So, within one year, we must be able to take one significant step forward.
TRL stands for terms that describe the Technology Readiness Level. TRL 1 is just a hypothesis. TRL 2 means there is already evidence for this technology, but nothing has been validated in practice yet. At the TRL 3 level, researchers are already able to show that the envisioned technology can work. Therefore, the goal of the first year in this study is to find out whether such an idea could work.
Within the scope of your research, you probably also need to cooperate with medical institutions. What is this cooperation like? Is there anything, such as doctor burnout/overload, that hinders this cooperation?
We cannot conduct any of these studies without cooperation partners in the clinic. Doctors are, of course, overworked, and participating in research is extra work for them. However, we have a very successful cooperation with the Breast Cancer Surgery Department of the Riga Eastern Clinical University Hospital (RAKUS). Doctors Prof. Jānis Eglītis and Kristaps Eglītis have been involved in our projects, helping to organize clinical trials in their clinic and enrolling patients in them. In the breast cancer and physical activity study, we had cooperation partners from RAKUS, as well as from the Latvian Academy of Sport Education, and from Norway, Lithuania, and Estonia.
You are operating in times of change, because by May 31, the scientific institution you represent must be merged with the Institute of Organic Synthesis. How will these changes affect your work?
These changes are felt more by the administration than by the scientists. We do not expect this merger to radically change our daily routine. I view the merger more as an opportunity to cooperate more actively and create joint projects with other researchers, especially chemists. It improves technical capabilities and broadens the scope of questions we will be capable of researching. So it is an opportunity that can be utilized, but one could also continue to operate just as we did when we were separate institutions. Overall, however, the mood is positive, and we expect that 1+1 will be more than 2.
Will the research be able to become broader and deeper?
Already within the framework of the consolidation, there was an opportunity to apply for projects where we could combine our expertise. These were special grants to promote cooperation between scientists from both institutions. Without much thought or effort, simply by talking about what one research group does and what the other does, we came up with a very coherent cooperation project idea. It has now concluded with interesting results.
The topic of the joint work was the delivery of peptide nucleic acids into cells using extracellular vesicles. Peptide nucleic acids are a synthetic DNA analog that can be used similarly to antisense oligonucleotides. One of the main problems hindering the active use of these molecules in therapy is that it is very difficult for them to enter the cell. In contrast, the extracellular vesicles we study are very widely used as drug delivery vehicles. In the study, we tried to ‘pack’ these peptide nucleic acid molecules into vesicles and use them to deliver them into cancer cells, which was successful. Consequently, for the first time, we demonstrated the possibility of delivering peptide nucleic acids into cells using vesicles, which further opens up broad opportunities to use them for the development of new therapeutic agents.