Mariella Filbin: Our latest paper on pediatric/AYA glioma

Mariella Filbin shared a post on X by Gustavo Cruzeiro about a recent paper by Ilon Liu et al. published in Cancer Cell.

“GABAergic neuronal lineage development determines clinically actionable targets in diffuse hemispheric glioma, H3G34-mutant”

Authors: Ilon Liu, Gustavo Cruzeiro, Lynn Bjerke, Chris Jones, Mariella Filbin et al.

“Very happy to announce our latest paper on pediatric/AYA glioma!

See tutorial from fantastic Gustavo Cruzeiro and Ilon Liu below – I’m so very proud of your resilience and dedication!

Biggest thanks to our fabulous collaborators from The ICR, Jones Lab ICR!! Chris, Rebecca, Lynn, Yura, Al – it was such a great joy working with you!!

A million thanks also to Michelle Monje for her unwavering support for this study, for always being my sounding board, and for the many fun G34-discussions and -dinners we had along the way.”

Quoting Gustavo Cruzeiro’s post:

“Our recently published manuscript in Cancer Cell – Diffuse hemispheric glioma, H3G34R/V-mutant (H3G34-DHG).

We resolve a putative hierarchy in H3G34-DHG along continuous interneuronal lineage development.

⁠H3G34-DHG tumor cells mirror spatial nests of human embryonal interneurons development.

Integrating our single-cell findings with genome-wide CRISPR screens, we show that interneuronal lineage progenitor states present a distinct vulnerability in H3G34-DHG.

Of these, we focus on CDK6 as a top screen hit and clinically actionable target.

H3G34-DHG tumor cells are more sensitive to these small molecules compared to other pediatric high-grade glioma subtypes.

⁠CDK6 targeting shifts H3G34-DHG towards more mature neuronal-like states and extends survival.

We report on a patient with progressive H3G34-DHG in whom treatment with a CDK4/6 inhibitor achieved 17 months of stable disease.

Thus, targeting CDK6 presents a promising avenue in H3G34-DHG for further translational study!

I want to thank all our collaborators, including lab mates at Mariella Filbin-Filbin Lab (Dana-Farber/Boston Children’s Cancer and Blood Disorders Center) and Chris Jones-Jones Lab ICR. I want to extend a special appreciation to our co-leads, Ilon Liu, Lynn Bjerke, and Rebecca Rogers.

A final thanks to the Alex Lemonade Stand Foundation, ‘A’ Award and Young Investigator, NIH Innovator Award (DP2), and the Sontag Foundation for supporting this work.”

Sources: Mariella Filbin/X and Gustavo Cruzeiro/X

Mariella Filbin is a Pediatric Oncologist at Boston Children’s Hospital and Dana-Farber Cancer Institute. She serves as an Assistant Professor at Harvard Medical School and is an Associate Member of the Broad Institute of MIT and Harvard.

Gustavo Alencastro Veiga Cruzeiro is a Research Fellow at both Dana-Farber Cancer Institute and the Broad Institute of MIT and Harvard. He is also the Co-founder and Head of Research and Development at NEOGENYS Molecular Diagnostics.