Evidence map›Paper›PMID 41857757›Full record

ArticleNeuro-oncology2026

RAC1 regulates Sonic Hedgehog-medulloblastoma growth via GLI-mediated transcription.

Nitish Jangde, Mi-Hye Lee, Luz Ruiz, Isabelle Egan, Anna M Jermakowicz, Rishika Chowdary, Jonathan Chu, Daniel T Wynn, Erik Goka, Marc Lippman and 2 more

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Article in Neuro-oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors.

Nitish JangdeLombardi Comprehensive Cancer Center, Georgetown University Medical Center, Georgetown University, Washington, DC, USA.ORCID 0000-0002-2768-4196
Mi-Hye LeeLombardi Comprehensive Cancer Center, Georgetown University Medical Center, Georgetown University, Washington, DC, USA.ORCID 0000-0002-5484-3383
Luz RuizLombardi Comprehensive Cancer Center, Georgetown University Medical Center, Georgetown University, Washington, DC, USA.
Isabelle EganLombardi Comprehensive Cancer Center, Georgetown University Medical Center, Georgetown University, Washington, DC, USA.ORCID 0009-0003-8876-9374
Anna M JermakowiczLombardi Comprehensive Cancer Center, Georgetown University Medical Center, Georgetown University, Washington, DC, USA.ORCID 0000-0003-3271-051X
Rishika ChowdaryLombardi Comprehensive Cancer Center, Georgetown University Medical Center, Georgetown University, Washington, DC, USA.
Jonathan ChuLombardi Comprehensive Cancer Center, Georgetown University Medical Center, Georgetown University, Washington, DC, USA.
Daniel T WynnLombardi Comprehensive Cancer Center, Georgetown University Medical Center, Georgetown University, Washington, DC, USA.ORCID 0000-0001-7447-4346
Erik GokaLombardi Comprehensive Cancer Center, Georgetown University Medical Center, Georgetown University, Washington, DC, USA.
Marc LippmanLombardi Comprehensive Cancer Center, Georgetown University Medical Center, Georgetown University, Washington, DC, USA.
David J RobbinsLombardi Comprehensive Cancer Center, Georgetown University Medical Center, Georgetown University, Washington, DC, USA.
Nagi G AyadLombardi Comprehensive Cancer Center, Georgetown University Medical Center, Georgetown University, Washington, DC, USA.ORCID 0009-0002-1994-3095

Funding

TRAINING GRANT IN TUMOR BIOLOGYT32CA009686 · NCI · GEORGETOWN UNIVERSITY · PI ANNA Tate RIEGEL, DAVID J ROBBINS · 1996 to 2026
$10.8M
Rac1 Inhibition for the treatment of medulloblastomaR21NS135506 · NINDS · GEORGETOWN UNIVERSITY · PI AYAD, NAGI G · 2024 to 2025
$429k
BellRinger Foundation at Lombardi Comprehensive Cancer Center of Georgetown UniversityCure Childhood Cancer 1305140Cure Childhood Cancer F31CA291046NCI NIH HHS T32 CA009686NIH HHS NS110591NIH HHS NS118023NIH HHS NS135506NINDS NIH HHS R21 NS135506
6 · The paper itself

Abstract

backgroundMedulloblastoma (MB) is the most common malignant brain tumor of childhood, and current treatments cannot sufficiently inhibit tumoral growth, leptomeningeal dissemination, and metastasis. Ras-related C3 botulinum toxin substrate 1 (RAC1), a low molecular weight GTPase involved in cytoskeletal regulation and cell migration, is established to facilitate tumorigenesis in other neoplasia, but RAC1 is unexplored in MB and has no targeted therapies.

methodsWe examined RAC1 activity in Sonic Hedgehog (SHH)-subtype MB using human and mouse Ptch1-/- cell models, RNAi knockdown, pharmacologic inhibition with GYS32661, transcript profiling, chromatin immunoprecipitation, and cytotoxicity assays in primary human astrocytes. We also determined the efficacy, brain penetration, and toxicity of GYS32661 in orthotopic spheroid Ptch1-/- mouse and rat models.

resultsRAC1 activity was markedly increased in the MB tissue compared to the normal cerebellum. RAC1 depletion suppressed the proliferation and migration of SHH-MB cells. Mechanistically, RAC1 regulated GLI1 and GLI2 expression and bound the upstream loci of GLI1 and DNMT1, revealing a novel mechanism of SHH transcriptional regulation. GYS32661, a brain-permeable RAC1 inhibitor, was not toxic to normal astrocytes, suppressed SHH-MB tumor growth, and improved survival in vivo without toxicity in rats.

conclusionRAC1 functions as a critical transcriptional regulator of SHH signaling and epigenetic mediators in medulloblastoma, highlighting its potential as a druggable target in SHH-dependent MB. Our findings also characterize the RAC1 inhibitor GYS32661 as a promising drug candidate for the treatment of SHH-MB.

Indexed as

Cerebellar NeoplasmsHedgehog ProteinsMedulloblastomarac1 GTP-Binding ProteinZinc Finger Protein GLI1AnimalsCell MovementCell ProliferationGene Expression Regulation, NeoplasticHumansMiceRatsTranscription, GeneticGLI1 protein, humanHedgehog Proteinsrac1 GTP-Binding ProteinRAC1 protein, humanSHH protein, humanZinc Finger Protein GLI1cell migrationcytoskeletonmedulloblastomaproliferationRAC1 GTPasetargeted therapy

Identifiers

PMID41857757
PMCPMC13233070

What Socratic holds

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LicenceCC BY-NC
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.