19 Aug 2020
Glioblastoma is the most common, aggressive, and invasive type of primary brain tumor, and there is currently a high, unmet need for more efficient therapies. In this video, Dr. Aleksandra Dukic, Institute for Cancer Research at Oslo University Hospital, discusses how she is using live-cell imaging to investigate novel gap junction inhibitors for use in limiting the invasion of glioblastomas into the brain and sensitizing these cells to chemotherapy.
My name is Aleksandra Dukic. I'm a postdoc in Kjetil Tasken group, here at the Institute for Cancer Research, which is a part of Oslo University Hospital in Norway. I'm a leader of an innovation project on novel treatment for a patient with glioblastoma, which is a SPARK Norway project.
Glioblastoma is the most common, aggressive, and invasive primary brain cancer, which is unfortunately lethal. There is high, unmet need for novel and more efficient therapies. We are developing protein-protein interaction inhibitors that will inhibit invasiveness of the glioblastoma into the brain, but also sensitize glioblastoma cells to temozolomide chemotherapy which is standard of care treatment.
And they will do so by inhibiting gap junctions. Currently, our focus is on the further developing our hit compounds. We derivatize the compounds and synthesize novel compounds, which we further characterize, and we hope that they will have better efficacy in vivo models.
Currently, some of the first hits and derivatized hits are being tested in vivo model of mouse glioblastoma. It is an orthotopic model where cancer cells are injected into the brain of mice, and then they are treated with our compounds locally at the sites, the brain.
We hope for at least with better efficacy than the standard of care, temozolomide treatment, which would be a very positive result for us. Some years ago, we developed a protein complex that has really [inaudible] the regulatory role in gap junction opening and closing. Knowing that, we wanted to develop an easy and fast, but also high-throughput assay where we can test our compounds.
We chose to use Incucyte in this purpose, because in that way, we can take images at a desire time point which are of good quality that we can further analyze and assess the effect of our compounds in inhibiting gap junction communication.
So we use the mentioned assay as a secondary screen, cell-base assay for testing and choosing our hit compounds. But for the rest of my glioblastoma project, I really cannot imagine the research without an Incucyte. We have an Incucyte ZOOM, and Incucyte S3 here at the institute, and I use both for my project.
Since our main interest is in glioblastoma invasion and migration as well as the formation and growth of glioblastoma spheres, it is very important to monitor cells over time, to take images at the desire time point which is what Incucyte enables us.
It also gives very good reproducibility, and it is easy to analyze. Our goal at the moment is getting preclinical in vivo proof of concept in mice. Achieving that will bring us to the whole new business world, how to place our new drug to the market.
Because glioblastoma is a terrible disease, we believe there is a shorter path to the clinic and easier way to reach clinical trials using our drug in combination therapy with the standard of care treatment.
University of Oslo
Aleksandra completed her Bachelor and Master’s degree in Molecular Biology at the University of Novi Sad, Novi Sad, Serbia in 2012, where she worked on cAMP signaling in testosterone-producing Leydig cells (Laboratory for Reproductive Endocrinology and Signaling). In 2013, she started her PhD at the University of Oslo in Kjetil Tasken group (Centre for Molecular Medicine Norway), focusing on A-kinase anchoring protein complex and regulation of gap junction intercellular communication. She obtained her PhD degree in Molecular cell biology at the Faculty of Medicine, University of Oslo in 2016. Aleksandra continued as a PostDoc in Tasken lab and applied knowledge from her PhD projects on an innovation, drug discovery project in cancer field, targeting gap junctions with small molecular compounds. The current project focuses on a novel target for inhibiting glioblastoma cancer invasion. The group is at present located in the Institute for Cancer Research, Oslo University Hospital.