New Drug Target Discovered for Treating Deadly Brain Tumor, Glioblastoma

    By Kathleen Berger, Executive Producer for Science and Technology

    Dr. Milan Chheda, MD, wants to be able to provide hope to his patients suffering from glioblastoma, the most aggressive and deadly brain tumor. Chheda is on the frontline in the battle against glioblastoma by actively leading research for new therapies and treating patients.

    “Most people will die within two years of being diagnosed,” said Milan Chheda, MD, neuro-oncologist and associate professor of medicine at Washington University School of Medicine in St. Louis.

    Research in his lab may one day lead to new and exciting therapies. Through collaboration with Li Ding, PhD, professor of medicine and genetics at Washington University School of Medicine, Chheda is now armed with groundbreaking discoveries that he can use to help his research efforts. Ding and her team successfully mapped the glioblastoma.

    “What their study does is apply multiple different layers, 10 different layers of looking at the tumor by taking a deeper look at the tumor microenvironment – not just the cell – but the surrounding cells that it interacts with,” said Chheda.

    It’s part of the Human Tumor Atlas Network, a large-scale effort to understand the life span of tumors. Single cell sequencing of glioblastoma and the tumor’s microenvironment led to the creation of 3D maps of the tumor ecosystem. Then the scientists analyze how the maps change over time, giving them valuable insights about glioblastoma.

    “The study found that not all glioblastomas are the same and they’re not going to respond in the same way to therapies,” explained Chheda.

    Mapping the tumor is helping Chedda develop new treatments to target and kill treatment resistant cells.

    “Trying to identify what makes cells within a specific patient different than other cells in that same patient,” said Chheda. “We’re trying to understand what makes some tumor cells resistant to the therapies we’re using and how can we target those cells in a better way. So what this study showed was that these other redundant new pathways that are driving the tumor have a central node – potential central hubs, networks – that can be used to turn off the entire system and not allow new pathways to allow the cell to grow. So that’s important because really what we’ve been doing in the field is trying to silence the networks from just hitting the outskirts, not the central “Death Star”, so to speak.”

    By using that Star Wars reference about the “Death Star”, Chheda said the reference helps people understand the node that was discovered and why building a strategy for attacking that ‘death star’ is critical in this race against the clock.

    “In terms of developing the therapies that target that ‘death star’, we have to show that there is a causal relationship that if the tumor has ‘this’ then it goes on to behave like ‘this’, said Chheda. “Now we know what to go after. Now we know what to target. But we have to prove it. But if you’re able to understand what makes the responders respond, then you can stratify your clinical trials in a much better way so that this group of patients is getting the appropriate treatment and this group of patients is getting a different treatment.”

    As studies continue, Chedda is hoping the findings will help match glioblastoma patients to experimental treatments for best patient outcomes.

    “Develop clinical trials where the drug that’s already out there is given to the right patient.” He said. “So really what we need are quick, testable biomarkers that says if you have ‘this result’, then you go into this bin.”