Dr. Bojana Stefanovska, at University of Minnesota Twin Cities, is a 2021 recipient of OCRA’s Ann and Sol Schreiber Mentored Investigator Award. Her project, “APOBEC3B and DNA Repair as Synthetic Lethal Combinations in CCOC,” explores DNA repair as a potential treatment avenue for clear cell ovarian carcinoma (CCOC).
My dad is a medical oncologist. When I was a child, he was doing his residency and I always thought what he was doing was so cool. We were hearing stories about people suffering from cancer all the time, and he was like a superhero to me.
I believe I was in middle school when he explained to me in words that I could understand about the Hallmarks of Cancer paper by Weinberg and Hanahan published in the 2000s. That sparked my curiosity, and I knew that I wanted to do something related to cancer. But rather than treating patients, I was more interested in understanding the biology behind this disease. Driven by that, I started my bachelor’s degree in molecular biology. And since the first day, I knew that I wanted to pursue a master’s degree and then a PhD, and I was certain that it had to be in cancer research.
I was always driven to learn more about cancers that affect the female population. My PhD work was completely based on breast cancer. And for my postdoc, I wanted to focus more on ovarian cancer, which is exclusively feminine cancer.
The major thing that drew me to ovarian cancer research is how sneaky this kind of cancer is. The symptoms are vague and non-specific, and women may feel them on any given day. Since they go unrecognized, that often results in delays in diagnosis and treatment. On the other hand, the treatments available are not perfect. And even though targeted therapies are already available that exploit unique features of cancer cells to attack them, there is so much more that can be done. There is still a lot to learn about the biology of ovarian cancer and how we can use that knowledge to effectively kill the cancer cells.
We all have this gene called APOBEC3B that is used to produce a protein that protects us when there is a particular viral infection. We don’t exactly know when and how, but in certain types of cancers, including ovarian cancer, it gets ‘woken up’ and instead of attacking the virus it attacks the human DNA by changing one of its building blocks. When that happens the structure of the DNA is damaged, and it needs to be repaired.
We all have very complex machinery that can identify the damage to the DNA and repair it. Try to think about it as bringing a broken car to the mechanics’ shop. They can typically spot the damage, repair it, and give it back to you ready to go. However, if the damage is too serious, the mechanics cannot do much and you will need to get rid of the car. Similar things can happen to your DNA. If there is too much DNA damage, the cells cannot repair. Instead, they surrender and die. In my project, I’m trying to use this feature in disfavor of the cancer cells. When they have their DNA damaged because they were attacked by APOBEC3B, I want to identify which “mechanic” can repair that damage, and then fire it, so that the cancer cells won’t be able to repair the damage and they will die.
The act of discovery is my biggest motivation. I find it fascinating that I can contribute to the understanding of the biology of cancer by discovering something that no one has ever discovered before and that it can complement the current understanding of things. It is like a never-ending story, but in a good way. The more knowledge you find, the more you realize that there is so much to be discovered, the more you want to do it. And if some of my discoveries can help change the practice of treating cancer one day, there won’t be a better reward than that.
I hope that in the following years we will find ways to improve screening and detection of ovarian cancer, but also improve and personalize the treatments even more.
If you had the opportunity to personally thank someone from the OCRA community who supported your work, what would you say?
I am very grateful that by investing in my project you believe that my research can change the way we treat ovarian cancer. This opportunity is very humbling and motivates me to work even harder to change for the better the future of patients suffering with ovarian cancer.