Inhibiting lethal glioblastoma invasion in the brain: Elucidating pathways with live-cell imaging

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.