bluuebunny/crossref_metadata_2025_split huggingface dataset:
EPEN-01. DISTINCT RELAPSE PATTERN ACROSS MOLECULAR EPENDYMOMA TYPES
Authors: Obrecht-Sturm Denise , Schoof Melanie , Eckhardt Alicia , Mynarek Martin , Gilbert Mark R , Adalpe Kenneth , Armstrong Terri S , Ramaswamy Vijay , Bockmayr Michael L , von Hoff Katja , Fleischhack Gudrun , Adolph Jonas E , Tippelt Stephan , Pfister Stefan M , Pajtler Kristian , Sturm Dominik , Drexler Richard , Ricklefs Franz L , Stephien Natalia , Gojo Johannes , Pietsch Torsten , Warmuth-Metz Monika , Kortmann Rolf-Dieter , Timmermann Beate , Haberler Christine , Rutkowski Stefan , Schüller Ulrich 
Published: June 2024

Abstract

BACKGROUND
Ependymoma (EPN) is not a uniform disease but represents different tumor types with biological and clinical heterogeneity. Some types have an excellent prognosis; others display frequent relapse. However, the pattern of when and where different types of EPN relapse is largely unknown.

METHODS
We assembled 552 intracranial EPN from pediatric (n=445) and adult (n=107) patients from European and Northern American cohorts and correlated DNA methylation patterns and copy-number alterations with clinical information. Median age at diagnosis was 13.4±18.8 (0.1 – 80) years.

RESULTS
In 271/552 (49.1%) of included EPN relapse occurred. First relapses occurred in the initial tumor bed in 70.9%, 22.4% were metastatic only, and 6.7% were combined local and metastatic. First relapses of PF-EPN-B (PF: posterior-fossa) and PF-EPN-SE (SE: subependymoma) occurred later than of PF-EPN-A, ST-EPN-YAP (ST: supratentorial), or ST-EPN-ZFTA (median time to relapse: 4.3 and 6.0 years vs. 1.9/1.0/2.5 years; p&lt;0.01). Metastatic or combined recurrences in PF-EPN-B and -A occurred more often in the spinal cord than in ST-EPN-ZFTA (75.0% and 40.0% vs. 12.5%; p&lt;0.01). In the latter, relapse occurred more frequently when harboring an alternative fusion or CDNK2A loss (p&lt;0.01, respectively). No distant relapses were observed in ST-EPN-YAP (n=9) or PF-EPN-SE (n=60). Post-relapse survival (PRS) was poor for PF-EPN-A and ST-EPN-ZFTA (5-year PRS: 44.5±4.4/ 47.8±9.1%), whereas PF-EPN-B and PF-EPN-SE displayed a 5-year PRS of 89.5±7.1/ 90.0±9.5% (p=0.03). However, 10-year PRS for PF-EPN-B dropped to 45.8±17.3%.

CONCLUSIONS
Relapse patterns of specific EPN types are different. Duration of surveillance and diagnostics should be planned incorporating entity-specific relapse information. Follow-up should be performed longer than 5 years after diagnosis. Spinal MRI should be considered as standard procedure during surveillance, particularly for PF-EPN-A, PF-EPN-B and ST-EPN-ZFTA.
EPEN-02. CAR T-CELLS TARGETED TO B7-H3 OR HER2 FUNCTION INDEPENDENTLY OF ANTIGEN DENSITY IN XENOGRAFT MODELS OF EPENDYMOMA
Authors: Mehta Sanya , Ibanez Jorge , Houke Haley , Emanus Erik , Ippagunta Siri , Mack Stephen C , Krenciute Giedre 
Published: June 2024

Abstract

BACKGROUND
Targeted treatment options are desperately needed for ependymomas (EPN). Chimeric antigen receptor (CAR) T-cells have immense potential to positively transform treatment outcomes; however, little is known regarding antitumor efficacy of CAR T-cells against EPNs. Specifically, antigen density has emerged as a major influencer of CAR T-cell potency. However, the specific high and low antigen density thresholds governing CAR T-cell efficacy for EPN are unknown. We hypothesize that antigen density heterogeneity governs CAR T-cell potency against EPN.

METHODS
Using quantitative flow cytometry, we determined antigen density of B7-H3 and HER2 (the two CAR targets currently in pediatric EPN clinical trials) on EPN patient derived cell lines (1425, ST1, CPITT, ST2, EPI, L46SJ). We generated second generation B7-H3 and HER2-CAR T-cells with CD28z signaling domain and compared long-term cytolytic activity, expansion, and cytokine production against EPNs.

RESULTS
We found that all EPN cell lines express remarkably high yet variable density of B7-H3 (6.3e4 – 3.4e5 molecules/ cell). In contrast, surface density of HER2 was consistently and significantly lower (860 – 2.5e4 molecules/ cell). In repeated-stimulation assays, B7-H3-CAR T-cells killed 7-10 times and expanded up to 325,360-fold when cultured against EPN. However, we observed no significant difference in total expansion or correlation with antigen density against EPNs. Surprisingly, expansion of HER2-CAR T-cells against EPNs was drastically higher (up to over 100-billion-fold) and greatly exceeded that of B7-H3-CAR-T cells against the same EPN cells despite much lower antigen density.

CONCLUSIONS
Our studies reveal significant antigen density heterogeneity of B7-H3 and HER2 in EPN, which may lead to target-specific impacts on CAR T-cell persistence. Indeed, results suggest that lower antigen density of HER2 may be superior for sustained CAR T-cell activity. Future work will validate whether HER-CAR T-cells have superior antitumor efficacy in vivo to further delineate role of antigen density thresholds in CAR T-cell potency.
EPEN-03. THE MANAGEMENT OF PEDIATRIC AND ADOLESCENT SPINAL EPENDYMOMA; A 20-YEAR NATIONAL EVALUATION INVOLVING UNITED KINGDOM PEDIATRIC ONCOLOGY PRIMARY TREATMENT CENTERS ON BEHALF OF THE UK CHILDREN’S CANCER AND LEUKAEMIA GROUP (CCLG)
Authors: Deghedy Marwa , English Martin , Curry Helen , Nicholson James , O’Hare Patricia , McCarthy Anthony , Uzunova Lena , Curry Sarah , Wilson Shaun , Jorgensen Mette , Thompson Dominic , Cox Rachel , Ronghe Milind , Brougham Mark , McAndrew Rachel , Lee Victoria , Bailey Simon , Thorbinson Colin , Goodden John , Picton Susan , Dias Sandra , Saeed Fozia , Srivatsa Kavitha , Ritzmann Timothy , Grundy Richard , Kilday John-Paul 
Published: June 2024

Abstract

INTRODUCTION
Pediatric spinal ependymomas account for approximately 1% of childhood CNS tumors. Most are myxopapillary ependymomas (MPEs). For symptomatic cases, maximal safe surgical resection is the accepted therapeutic standard. However, a role for adjuvant therapy is unclear, underpinned by low incidence rates, inadequate trial data and recent WHO upgrading of the MPE variant. This retrospective national service evaluation aimed to provide safety and outcome data, from which future management guidance could be developed.

METHOD
Children, teenagers and young adults diagnosed with a spinal ependymoma of any WHO grade since 2000 across 17 UK CCLG centres were evaluated. Patient demographics, therapies, adverse events, and outcomes were captured.

RESULTS
102 patients were evaluated. Ten children had NF2 (median age 11 (7.6 – 14) years) with nine located in the cervicomedullary region. All ten patients were alive following surveillance (n=3) or surgical intervention (n=7) with an estimated median PFS of 5.4 (1.7 – 9.1) years. For the remaining 92 patients (median age 12 (0.7 – 19) years), 63% of tumors were lumbosacral, 73% demonstrated MPE morphology and 16% were metastatic. The median symptom interval was 4 (0 - 36) months. Progression or relapse was reported in 30/92 (33%), with a 5-year PFS of 62(+ 6)%, yet only 4 disease-related deaths occurred (mean follow-up 6.8 years; no MPEs). Across this non-NF2 cohort, gross/near total resection and upfront adjuvant radiotherapy independently reduced disease progression risk (p &lt; 0.05). However, improved local control from early irradiation was not statistically proven when localized disease or MPEs were exclusively scrutinized. No radiotherapy-related high-grade toxicity was reported.

DISCUSSION
Pediatric spinal ependymomas are rare tumors demonstrating excellent survival, particularly MPEs. Maximal safe surgery and early adjuvant radiotherapy can improve local control rates, but European collaboration will be required to evaluate efficacy for certain tumor and clinical subgroups. Conclusions could support future national management guidelines.
EPEN-14. MOLECULAR MARKERS AND PREDICTORS OF OUTCOME FOR PAEDIATRIC INTRACRANIAL EPENDYMOMA IN THE PROSPECTIVE, MULTICENTRE E-HIT2000 TRIAL AND SUBSEQUENT HIT-REGISTRIES: A POOLED ANALYSIS OF 244 PATIENTS
Authors: Ghasemi David R , von Hoff Katja , Obrecht-Sturm Denise , Wenning Janna , Mynarek Martin , Gerber Nicolas U , Benesch Martin , Juhnke Björn O , Bison Brigitte , Warmuth-Metz Monika , Timmermann Beate , Faldum Andreas , Fleischhack Gudrun , Grotzer Michael , Driever Pablo Hernáiz , Beilken Andreas , Ebinger Martin , Graf Norbert , Frühwald Michael , Schmid Irene , Koch Arend , Bergmann Markus , Hagel Christian , Coras Roland , Blümcke Ingmar , Reifenberger Guido , Felsberg Jörg , Keyvani Kathy , Harter Patrick N , Prinz Marco , Staszewski Ori , Acker Till , Brück Wolfgang , Hartmann Christian , von Deimling Andreas , Sommer Clemens , Hasselblatt Martin , Riemenschneider Markus J , Monoranu Camelia-Maria , Rushing Elisabeth , Kool Marcel , Pfister Stefan M , Schüller Ulrich , Pietsch Torsten , Kortmann Rolf D , Kwiecien Robert , Witt Hendrik , Pajtler Kristian W , Rutkowski Stefan 
Published: June 2024

Abstract

BACKGROUND
Throughout the past decade, molecular tools have revolutionised ependymoma classification, yet their application has been limited in clinical trial cohorts.

METHODS
We present the molecular analysis of paediatric ependymoma patients from the E-HIT2000 trial (n = 165), or subsequent HIT2000-interim and I-HIT-MED registries (n = 79) based on DNA-methylation profiling with multi-level classification using the Heidelberg Brain Tumor Classifier v12.5 and the analysis of chromosome 1q, 6q, and CDKN2A copy number status. Prior to further analysis, cases without ependymoma group prediction were excluded (n = 16/244).

RESULTS
5-year PFS and OS rates varied by group: EPN-PFA (n=146/228) 45±4% and 76±4%; EPN-PFB (n=19/228) 90±7% and 100%; EPN-ZFTA (n=59/228) 63±7% and 87±5%; and EPN-YAP1 (n=4/228) 50±25% and 100%. EPN-PFA was subclassified into nine subtypes. Poor median PFS was observed for PFA1c (n=22, 5-yr-PFS 32±10%/5-yr-OS 77±9%), PFA1d (n=13, 35±14%/72±14%), PFA1e (n=15, 47±13%/59±13%), and PFA2a (n=16, 27±12%/50±14%). Presence of 1q gain was associated with inferior survival (n = 39/146, 29±8%/65±8%). 6q loss impacted PFS, but not OS (n=8, 25±14%/100%). Among 59 EPN-ZFTA cases, 46 clustered with EPN ZFTA-RELA fused, and 12 clustered within recently described subgroups of EPN-ZFTA (EPN-ZFTA alt., Cluster 1: 1/12, Cluster 2: 11/12). Strikingly, 6/11 EPN ZFTA-alt. (Cluster 2) cases showed infratentorial (4/6) or supratentorial midline location (2/6). Homozygous deletion of CDKN2A (CDKN2A-/-; n=8) was only observed in EPN ZFTA-RELA. Presence of EPN ZFTA-alt. (cluster 2) (5-yr-PFS: 36±15%; p&lt;0.001), and CDKN2A-/- (19±16%; p&lt;0.0001) was associated with inferior PFS compared to EPN ZFTA-RELA CDKN2A-wt (81±6%). OS was only impacted for patients with EPN ZFTA-RELA CDKN2A-/- (5-yr-OS: 38±20%, p&gt;0.0001).

CONCLUSIONS
We present strong evidence supporting the inclusion of molecular criteria into the next generation of clinical trials for children with ependymoma.
EPEN-15. TRANSCRIPTOMIC AND METABOLOMIC INTEGRATION REVEAL INTRA-TUMOUR HETEROGENEITY AND IDENTIFY DISULFIRAM AND COPPER AS A SYNERGISTIC THERAPY IN PAEDIATRIC EPENDYMOMA
Authors: Pandele Alina , Whitby Alison , Lankford Sophie J , Macarthur Donald , Kamaly-Asl Ian , Barrett David , Grundy Richard , Kim Dong-Hyun , Rahman Ruman 
Published: June 2024

Abstract

BACKGROUND
Ependymoma (EPN) is the second most malignant paediatric brain tumour. The PF-A subgroup, associated with a hypoxic microenvironment, has a dismal survival rate of 50% with clinical trials failing to demonstrate a significant survival advantage from chemotherapy to date. As the lack of genomic alterations makes it difficult to uncover novel therapeutic targets, we present a multi-omic integration investigating whether spatially-distinct tumour microenvironments represent targetable metabolic niches in PF-A EPN.

METHODS
Surgical sampling of spatially-distinct regions was performed on eight PF-A EPN patients. Metabolites and RNA were simultaneously extracted from the same cellular population and analysed using liquid chromatography-mass spectrometry (LC-MS) and RNAseq. Multi-omic integration was performed using Metscape3 and functional assays evaluating proliferation, invasion and siRNA-mediated knockdown were performed in 2D and 3D models of intra-tumour region patient-derived cell lines. Selected single and drug combination therapy was performed in normoxia and hypoxia, and synergy assessed using the Chou-Talalay method.

RESULTS
Multi-omic integration revealed 124 dysregulated metabolic pathways, encompassing 156 genes and 49 metabolites with the largest number of interactions occurring in the gluconeogenesis pathway. Each anatomical region also presented at least one unique gene-metabolite interaction demonstrating heterogeneity within and across PF-A EPN tumours. Four selected drug targets (Disulfiram, Vandetanib, Mildronate and FBP1 inhibitor) based on metabolically relevant genes (ALDH3A1, FMO3, BBOX1, FBP1) showed impairment of metabolic viability in vitro, with limited chemosensitivity observed in control human cerebellar astrocytes. The addition of Cu2+ significantly sensitised cells to Disulfiram, particularly under hypoxic conditions. This synergistic combination significantly impaired invasion in both normoxia and hypoxia.

CONCLUSION
This is the first instance where multi-omic data integration and intra-tumour heterogeneity has been investigated for paediatric EPN revealing novel therapeutic targets in the context of gene-metabolite correlations. Drug tolerability will be further assessed in vivo using the previously characterised PF-A EPN orthotopic mouse xenograft MAF-928.
EPEN-16. BULK AND SINGLE-CELL SPATIAL CHARACTERIZATION OF THE TUMOR IMMUNE MICROENVIRONMENT OF POSTERIOR FOSSA GROUP A EPENDYMOMAS
Authors: Lammers Julie A S , Kranendonk Mariëtte E G , Calkoen Friso G , van den Broek Thijs J M , Federico Aniello , Kool Marcel , Hoving Eelco W , Wesseling Pieter , Kester Lennart A , van der Lugt Jasper 
Published: June 2024

Abstract

BACKGROUND
Despite advancements in molecular classification of ependymomas, the tumor immune microenvironment of posterior fossa group A (PFA) ependymomas and the spatial interplay between tumor and immune cells have not been elucidated. Here, we aim to comprehensively characterize the tumor immune microenvironment of pediatric PFA ependymomas, which could ultimately uncover leads for immunotherapy for these children.

METHODS
We collected bulk RNA-sequencing data of 28 PFA ependymoma samples and defined two subgroups based on the expression of immune-related genes (n = 716). Furthermore, we analyzed single-cell RNA-sequencing data of PFA ependymomas to dissect myeloid and lymphocyte heterogeneity, which we subsequently used to deconvolute bulk data. Lastly, we performed both high-dimensional cyclical immunofluorescence of 20 protein markers on a tissue microarray containing 60 cores from 20 tumor samples and immunohistochemistry on whole tissue slides.

RESULTS
Unsupervised hierarchical clustering of bulk RNA expression of immune-related genes revealed the presence of an immune-enriched subgroup. Furthermore, analysis of single-cell RNA-sequencing data identified multiple distinct myeloid cell subpopulations, with gene expression signatures reflective of inflammation, angiogenesis/hypoxia response and proliferation. Deconvolution of the bulk RNA-sequencing data using the newly annotated single-cell data as a reference showed enrichment of both myeloid cells and lymphocytes in the immune-enriched subgroup. Lastly, spatial immune profiling enabled detailed mapping of the organization of the tumor immune microenvironment and unveiled a heterogeneous presence of myeloid cells, with enrichment of infiltrating myeloid and T-cells in peri-necrotic areas compared to areas with high tumor cell density.

CONCLUSIONS
Our multi-faceted approach has shed unprecedented light on the cellular and spatial heterogeneity within the PFA ependymoma immune microenvironment. Further studies are warranted to unravel the functional differences between the two subgroups and the potential impact on response to future immunotherapeutic approaches/interventions.
EPEN-19. IMPACT OF MOLECULAR SUBTYPING ON PROGNOSIS IN CHILDREN AND ADOLESCENTS WITH SPINAL EPENDYMOMA
Authors: Engertsberger Lara , Benesch Martin , Mynarek Martin , Tonn Svenja , Obrecht-Sturm Denise , Perwein Thomas , Stickan-Verfürth Martina , Funk Angela , Timmermann Beate , Claviez Alexander , Kortmann Rolf-Dieter , Riemenschneider Markus J , Pietsch Torsten , Bison Brigitte , Warmuth-Metz Monika , Pajtler Kristian W , Rutkowski Stefan , Schüller Ulrich 
Published: June 2024

Abstract

PURPOSE
Ependymomas of the spinal cord are rare among children and adolescents, and the individual risk of disease progression is difficult to predict. Recent advances in subtyping the main molecular groups, myxopapillary ependymoma (MPE) and spinal ependymoma (SP-EPN), have successfully identified distinct risk groups among adult patients. This study aims at evaluating the prognostic impact of MPE subtypes A and B in a pediatric cohort.

METHODS
Eighty-three patients with spinal ependymoma ≤22 years registered in the HIT-MED database between 1992 and 2022 were included. Forty-seven tumors were analyzed regarding global DNA methylation. In six cases, antibodies against HOXB13 and MYCN were used as surrogate markers for the methylation group. Twenty-eight MPE were further classified into subtypes by t-distributed stochastic neighbor embedding (t-SNE) analysis.

RESULTS
MPE (n=32, 63%) was the most common molecular type followed by SP-EPN (n=17, 33%) and MYCN-amplified ependymoma (n=2, 4%). One case remained molecularly unclear, and one was excluded due to reclassification as anaplastic pilocytic astrocytoma. MPE subtyping identified 18 MPE-A and 9 MPE-B (inconclusive: n=1). 5-year progression-free survival (5y-PFS) did not significantly differ between MPE and SP-EPN (65% vs. 78%, p=0.64). MYCN-amplification was associated with early relapses and with death in one patient. Patients with MPE-B may have a tendency towards superior 5y-PFS compared to MPE-A (86% vs. 56%, p=0.15), irrespective of the use of adjuvant treatment. MPE-A was more frequently disseminated at time of diagnosis (n=6/18) than MPE-B (n=1/8, not evaluable: n=1; p=0.28).

CONCLUSION
Molecular subtyping of spinal ependymoma in children does not allow to separate patients into distinct risk groups, yet. However, the potentially favorable PFS among patients with MPE-B prompts the consideration of treatment de-intensification for this group. Larger cohorts and further insights into the molecular heterogeneity of these tumors are needed to complete the basis for future clinical decision-making.
EPEN-20. LEVERAGING ABERRANT EXTRACELLULAR VESICLE SIGNALING FOR TARGETED DRUG REPURPOSING IN PEDIATRIC EPENDYMOMA
Authors: Maass Kendra K , Rettenmeier Johanna , Sundheimer Julia K , Roosen Mieke M , Volz Stefanie , Wedig Tatjana , Ertel Paula , Gansert Cornelia , Richter Karsten , Nessling Michelle , Peterziel Heike , Friedenauer Aileen , Herter Sonja , Oehme Ina , Scheuermann Sophia , Seitz Christian , Senfter Daniel , Benzel Julia , Mueller Torsten , Okonechnikov Konstantin , Genard Geraldine , Krijgsveld Jeroen , Pfister Stefan M , Pajtler Kristian W 
Published: June 2024

Abstract
Increasing evidence highlights the diverse functions of extracellular vesicles (EVs) as intercellular messengers in all facets of cancer progression, pointing towards a potential new avenue in cancer treatment. Limited understanding of tumor-specific deregulations and lack of suitable drug compounds have hampered clinical translation of targeted interference with EV signaling. The most aggressive types of intracranial ependymoma (EPN) in children and adults are resistant to chemotherapy. Despite enormous diagnostic advancements in classification and stratification, EPN lack recurrent effective molecular targets precluding access of affected patients to precision-based oncology therapeutics. Here, we characterized the proteome of ninety-five EPN and five matching healthy control brain tissue samples. Employing a mulit-omic data integration approach, we identified EVs as an excessively augmented pathway on the functional level. Isolation and molecular characterization of EPN EVs combined with single cell sequencing analysis, and ultra-high content imaging unraveled perivascular mesenchymal cell populations as predominant EV originators. Targeting EV pathways through chemical inhibition of sphingomyelinases (SMPD1, SMPD2, SMPD3) including re-purposed FDA approved compounds revealed growth inhibition, reduced invasion capacity in vitro and significant survival probability in vivo. Transcriptomic analysis and scanning electron microscopy delineated transition of mesenchymal-to neuroepithelial subpopulations in cells and patient-derived xenograft (PDX) models of EPN upon reduction of EV release. This study showcases the inhibition of EV signaling as a promising therapeutic strategy against mesenchymal tumor persister cells, which are the suspected origins of repeated EPN relapses. Our study provides a framework to leverage cell state-specific vulnerabilities and drug repurposing to attack the most aggressive cell populations in cancers with unfavorable prognosis.
EPEN-22. ZFTA FUSION ONCOPROTEINS DRIVE ONCOGENESIS THROUGH ASSEMBLY OF BIOMOLECULAR CONDENSATES
Authors: Varadharajan Srinidhi , Arabzade Amir , Shirnekhi Hazheen K , Ippagunta Siri , Laboe Nic , Gee David , Emanus Erik , Kardian Alisha , Phillips Aaron H , Tripathi Swarnendu , Shirinifard Abbas , Petersen Becky , King Sharon , Stabley Daniel , Pitre Aaron , Campbell George , Park Cheon-Gil , Durbin Adam D , Qi Jun , Bertrand Kelsey , Taylor Michael D , Northcott Paul A , Deneen Benjamin , Ansari Aseem Z , Kriwacki Richard W , Mack Stephen C 
Published: June 2024

Abstract

BACKGROUND
Ependymomas continue to be an aggressive brain tumor entity without targeted therapies. The highly recurrent fusion oncoprotein (FO), ZFTA-RELA, is known to be associated with about 70% of supratentorial ependymomas. While recent studies have highlighted that the fusion protein is involved in aberrant DNA binding and subsequent oncogenic gene expression, the precise mechanisms underlying the transcriptional dysregulation remain elusive.

METHODS
Using super-resolution and lattice-sheet microscopy, we demonstrate that ZFTA-RELA forms dynamic liquid-like nuclear condensates. ZFTA-RELA condensates recruit co-factors like Med1, and Brd4 and are associated with the transcription of ependymoma oncogenes (Notch1 and Ccnd1). We leveraged machine learning models trained on FOs in other cancers to identify critical intrinsically disordered domains (IDRs) within ZFTA-RELA. A series of mutagenesis experiments were conducted to determine IDRs important for condensate formation, transcription, and tumor initiation. We also performed NMR spectroscopy to unravel the protein structure of ZFTA-RELA zinc finger binding domains.

RESULTS
We demonstrate that transcriptional condensate formation of ZFTA-RELA is an important cellular phenotype that is tightly linked with oncogenic transcription and tumor initiation. Further, we identify key residues within the zinc finger domain of ZFTA that are required for DNA binding of oncogenic target genes and condensate formation. Deletion of the key IDRs within ZFTA-RELA disrupts condensates and abolishes transcriptional activation and tumorigenesis. We also show that condensate formation is an underlying feature found across all other ZFTA-fusion oncoproteins, providing a model to understand how ZFTA FOs drive cancer.

CONCLUSION
Our studies provide mechanistic insights into the biophysical and structural basis of ZFTA fusion oncoproteins. These findings provide a framework to develop druggable strategies through targeting ZFTA FO zinc finger domains or disruption of oncogenic condensates.