Giorgio Seano: Why Does Glioblastoma Always Outsmart Treatment?
Giorgio Seano, Group Leader of the Tumor Microenvironment Lab at Curie Institute, Paris-Orsay, shared a post on Bluesky about a paper he co-authored with colleagues published in Neuro-Oncology:
“Why does glioblastoma always outsmart treatment?
In our Neuro-Oncology paper, we identified proneural-mesenchymal hybrid glioblastoma cells that are resistant to therapy and dependent on nuclear import. Short walkthrough below. Let’s dive in!
Using dual fluorescent reporters for proneural and mesenchymal states, we tracked live patient-derived glioblastoma lines and uncovered a hybrid population expressing both signatures… let’s talk about an identity crisis!
These hybrid cells don’t just look different, they proliferate like they’re on Red Bull and shrug off DNA damage after irradiation. Have they got superhuman repair skills?
Therefore, these cells are resistant to treatment and are linked to a poorer patient prognosis. Using RNA-seq, nuclear proteome and scChIP-Seq, we discovered their Achilles’ heel: a hyperactive nuclear transport system they rely on to import oncogenes like MYC and maintain their state.
Here’s the exciting part: we can target this vulnerability.
We hit them with importazole (import blocker) and selinexor (export inhibitor).
Targeting nuclear import decreases the hybrid cell pool and enhances chemoradiation sensitivity, opening a new therapeutic avenue against GBM.
Huge congrats to Guillaume Bourmeau, leading author and my brilliant PhD student, for spearheading this work on GBM hybrid cells at the Curie Institute! Your dedication made this breakthrough possible.
This research wouldn’t have been possible without the work of Oceane Anezo, Jeremy Raymond, Alberto Ballestín, Cathy Pichol-Thievend, Juliette Reveilles, Adrien Thomas, Valentino Ribecco, and the collaboration with Celine Vallot, Gaetano Gargiulo, Vidhya M. Ravi, and Kevin Joseph.
Special thanks to EANO for sharing our work, and heartfelt gratitude to the European Research Council (ERC), ARC Foundation for Cancer Research, Curie Institute, and CNRS Biology for their generous support.
You can dive into all the multi-omics data and findings in the full paper.”
Title: Proneural-Mesenchymal hybrid glioblastoma cells are resistant to therapy and dependent on nuclear import
Authors: Guillaume Bourmeau, Oceane Anezo, Jeremy Raymond, Alberto Ballestín, Cathy Pichol-Thievend, Juliette Reveilles, Adrien Thomas, Lin Wang, Melanie Miranda, Eve Moutaux, Stephane Liva, Valentino Ribecco, Laetitia Besse, Florent Dingli, Damarys Loew, Celine Vallot, Gaetano Gargiulo, Vidhya M Ravi, Kevin Joseph, Giorgio Seano
You can read the Full Article in Neuro-Oncology.
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