Progress and Promise in Brain Tumor Research (Podcast)

Single-cell RNA sequencing, the microbiome and more offer insight into complex brain tumors

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The mean life expectancy for patients with glioblastoma — the most common primary malignant brain tumor in adults — is 15 to 18 months. But there’s hope on the horizon thanks to work being done by researchers such as Justin Lathia, PhD.

“Harnessing a lot of new knowledge, whether it’s single-cell sequencing or exploding understanding of the microbiome and how it modulates disease, is going to provide opportunities to develop the next generation of therapeutic interventions,” says Dr. Lathia, Scientific Director for Cleveland Clinic’s Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center and Co-Director of the Center of Excellence in Brain Tumor Research and Therapeutic Development in Cleveland Clinic’s Lerner Research Institute.

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In the latest episode of Cleveland Clinic’s Neuro Pathways podcast, Dr. Lathia discusses new research in the field and delves into the following:

  • Why immunotherapies have been ineffective in treating brain tumors
  • The potential of single-cell RNA sequencing to provide insight into brain tumors
  • The role of myeloid-derived suppressor cells in glioblastoma
  • Differences in glioblastoma in males and females
  • The effect of the microbiome on tumors

Click the podcast player above to listen to the episode now, or read on for a short edited excerpt. Check out more Neuro Pathways episodes at clevelandclinic.org/neuropodcast or wherever you get your podcasts.

Excerpt from the podcast

Dr. Lathia: Single-cell RNA sequencing has given us a lot of insight into what we call the cellular heterogeneity. Single-cell profiling is allowing us to understand the extent of this heterogeneity, and it’s really helping us stitch together the whole picture. And there’s some fancy bioinformatics that can be applied to it that will allow us to predict things like mutational trajectories or lineage relationships and really put the pieces of plasticity together.

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There’s a collection of papers that came out in the February 2021 issue of Nature Cancer that all went at this a little bit differently. We were asked to write the News & Views section. There, we put the three papers together, and what the single-cell sequencing has shown is that there are differences in programs. Some tumors rely on wound healing genetic programs, some on developmental programs. There are differences in metabolism. So, some tumors are relying on different metabolic pathways versus others. And this is being traced down to the single-cell level. I think this higher resolution is actually allowing molecular targets to be identified. It’s very promising.

My speculation is that we have so many drugs that target so many pathways – and very few of them were even developed or thought of for brain tumors. So we have a whole toolbox. Once we know the pathways, the programs and the networks that need to be targeted, I think we have an opportunity.… The more information we have about these tumors, the more molecular targets we may end up with.