Allow me to congratulate you for being the recipient of the 2024 EU Contest for the Young Scientists EuChemS Award. Can you briefly introduce yourself, and tell us what has drawn you towards science, and entering the European Union Contest for Young Scientists (EUCYS)?
Thank you very much. It is such honour to be awarded this prestigious price.
My name is Janis Bojko, I am a student of the 2nd year of the Bachelor’s degree programme in Bioorganic Chemistry and Chemical Biology at Palacký University in Olomouc/Czech Republic. I am currently working in the research group of Dr. Petr Cankar on the synthesis of new CDK2 inhibitors, also in the context of cancer treatment. In my free time I like to read, hike and collect minerals.
What did you think of the competition, now that you participated? How would you summarise your experience?
Participating in EUCYS was my first big professional experience abroad, so the fact of participation itself meant a lot to me. I had the opportunity to meet inspiring people from all over the world. I am still in contact with some of them. The presentation of the project in English was a very enriching experience. It certainly gave me an insight into future aspects of where to focus my attention in the context of my studies.
Can you briefly explain the science behind your project and how the selective-dual inhibitors work to target the CDK4/6 and FLT3-ITD protein complex?
The issues that my project focused on were straightforward from a synthetic chemistry perspective.
In the treatment of acute myeloid leukaemia, it has been found that blocking the CDK4/6 complex (a biological target in breast cancer treatment) makes both the prognosis and the treatment itself more effective. For this reason, this research focused on whether the combination of structural motifs (i.e. parts of molecules) from the CDK4/6 inhibitor, Palbociclib, and the experimental inhibitor for the treatment of acute myeloid leukaemia, AMG 925, would lead to an increase in the biological activity of the compound against the target cancer cells.
The mechanism of action is illustrated by the analogy of a lock and key. Imagine that in the human body you have billions of locks (CDK4/6 and many other proteins) and only one key (synthesized drug) to them. The task of the key is to get only to the selected lock in the shortest possible time. This is exactly an example of how extremely challenging it is to design a selective drug that will have as few side effects as possible.
Let us now focus on the actual issue surrounding FLT3-ITD. FLT3 is a receptor tyrosine kinase that is very important for the development of haematopoietic stem cells. An average of 40% of patients suffering from acute myeloid leukemia have internal tandem duplication (ITD), which is associated with a poor prognosis, shorter remission duration and higher relapse rates, compared to patients who do not suffer from ITD.
These and many other reasons are the main motivation to gain more awareness and knowledge in the context of this disease.
My task was to perform synthetic preparation of all substances intended for biological testing. This required learning the various analytical methods and approaches necessary for such work.
Why did you choose to focus your research on this particular area, specifically on acute myeloid leukaemia (AML)?
My main goal was to get to the beginning of the whole process, namely the organic synthesis – the preparation of substances as such. For this reason, I applied for a pre-announced project in Dr. Petr Cankar’s research group, which has been working on this topic for a long time.
The whole topic was very attractive because it had two counterpoints that interested me at the time of selection. On the one hand, hard organic synthesis, which included also analytical and separation methods. On the other, subtle but very important information from the cell and molecular biology side.
What was important to me at the time was that this was a medicinal chemistry project that could provide more information about a specific disease or its treatment options.
What are the next steps for testing and developing these compounds for potential cancer therapies?
The journey of a drug from a university laboratory to the hands of doctors and their patients is a very thorny one. Basically, the substance first needs to have absolutely exceptional biological activity. This seems like a detail, but many pharmaceutical companies have poured billions of dollars into this first step and never even got there.
So, the first step would be to prepare a sufficiently high number of compounds and, based on in vitro testing (tissue culture testing), select those compounds that perform best. The most active candidates would then undergo in vivo testing (mice, rats, rabbits) to determine how the drug is metabolised. Only after it has been verified that the substance is not toxic to the body can a human clinical study be carried out in three phases. This whole process takes an average of 12-15 years, so it is a very time-consuming and financially demanding with no certain outcome.
The aim of the project was not to bring new drugs to the market, but to investigate whether the structural combination of two unique compounds would lead to a positive change in biological activity. When all the selected compounds were tested, higher biological activity was found for a compound for which this was not expected.
In the context of future developments, this is valuable for the synthesis of new compounds in this group.
The value of the data obtained lies in the synthetic methods developed – syntheses can be performed without the need for parameterization and also in the structure of the compounds – we know how to design compounds structurally to have the highest biological activity.
What are your future plans? Do you see yourself working on this topic further?
I am currently working towards becoming a successful university graduate. Thanks to EUCYS, I will be attending EXPO 2025 in Osaka, which I am really looking forward to.
In the summer I would like to go on a practical internship abroad, in order to collect new experiences and gain new perspectives and ideas that will be invaluable in the future.
In the foreseeable future, I would like to study in the North where they do chemistry, which interests me.
I’ll see what specific direction I take in the future. Medicinal chemistry is a very promising field, no doubt about it. Its logical disadvantage is that the substances you synthesize must be exceptionally active to be successful. I would like to explore a methodology of organic synthesis that is directly applicable to the synthesis of biologically active compounds.
There are many plans. I’ll see what the future holds.
Do you have any advice for your peers who may be interested in science?
Choose an area that interests you and that you think you will enjoy in the future. Don’t be afraid to fail and don’t lose hope if you don’t succeed – that’s what science is all about. Choose the internship/project led by the supervisor you think will teach you the most and give you the most information. Take advantage of opportunities where you can meet similarly science-oriented peers. Another important aspect to mention is not to forget about your personal life. I would say this is kind of an A-Q for me, which I have unconsciously followed. Just don’t lose the drive.
We usually ask scientists interviewed here if they have any advice to give to young, early career researchers. Now, let me turn this around: as a young scientist, do you have a message for those researchers who are on the field for a long time already?
Most of the people who have been long in science have only gotten to such places because of their excellent work. Don’t fall into lethargy, keep doing your work with enthusiasm and drive for the field. Be open to your students’ ideas and support them so that they can one day stand at the same level or even higher than yourself. I would like to give all respect to you, our world would not look the way it does were it not for your innovative work.
This interview is approaching the end – would you like to share any final thoughts?
I would like to thank everyone who supported me, especially my family, friends and the team of Petr Cankar’s research group, especially Monika T., Lukáš J., David P., Radoslav S.
