BRAINTOX Uremic Toxins in Chemotherapy Response in the Brain

Glioblastoma is amongst the most aggressive and fast-growing brain cancers. Currently, there are no effective treatments and most patients only live about 14 months after being diagnosed. One of the main challenges in treating glioblastoma is that the tumor can change how it gets its energy, which helps it grow quickly. In addition, each patient responds very differently to cancer treatment making it difficult to develop a single effective treatment. Therefore, understanding how the tumor changes its metabolism can help us find the best treatment for each individual patient. In a recent study we found surprisingly high levels of certain substances called uremic toxins (like p- cresyl sulfate and indoxyl sulfate) in brain tumor tissue. These toxins are usually found in urine and are not supposed to build up in other parts of the body. Within the FWF 1000 ideas program, we are exploring a new idea: that these uremic toxins might be taken up by brain tumor cells and affect how patients respond to treatment. To test this idea, we will use advanced techniques to see in which regions of the brain tumor uremic toxins accumulate and how tumor cells incorporate them into their metabolism. We are also testing how these uremic toxins affect the effectiveness of cancer treatment. To investigate it, we will use fresh tumours removed from patients by surgeons at the Medical University of Graz. At the CBmed laboratories, these tumours are used to grow individual patient derived cells which can be tested with a combination of uremic toxins and cancer treatments in a specialized device. Additionally, in collaboration with Joanneum Research we will investigate the effect of uremic toxins in a mouse model of glioblastoma. All together, these experiments will provide information on whether uremic toxins improve or worsen the response to cancer treatment and will move us one step forward towards using personalized medicine for treating cancer.