NFDI4DS | UHH-SEMS - Publication Details

Clinical Efficacy of ONC201 in H3K27M-Mutant Diffuse Midline Gliomas Is Driven by Disruption of Integrated Metabolic and Epigenetic Pathways

OPENALEX - Publications

Sriram Venneti Abed Rahman Kawakibi Sunjong Ji Sebastian M. Waszak Stefan R. Sweha and 79 more

Abstract Patients with H3K27M-mutant diffuse midline glioma (DMG) have no proven effective therapies. ONC201 has recently demonstrated efficacy in these patients, but the mechanism behind this finding remains unknown. We assessed clinical outcomes, tumor sequencing, and tissue/cerebrospinal fluid (CSF) correlate samples from patients treated two completed multisite studies. following initial radiation prior to recurrence a median overall survival of 21.7 months, whereas those after had 9.3...

10.1158/2159-8290.cd-23-0131 article EN cc-by-nc-nd Cancer Discovery 2023-08-11

Excess ω-6 fatty acids influx in aging drives metabolic dysregulation, electrocardiographic alterations, and low-grade chronic inflammation

OPENALEX - Publications

Vasundhara Kain Kevin A. Ingle Maureen Kachman Heidi Baum Gobinath Shanmugam and 3 more

Maintaining a balance of ω-6 and ω-3 fatty acids is essential for cardiac health. Current in the American diet have shifted from ideal ratio 2:1 to almost 20:1; while there body evidence that suggests negative impact such shift younger organisms, underlying age-related metabolic signaling response excess influx incompletely understood. In present study, young (6 mo old) aging (≥18 mice were fed 2 with ω-6-enriched diet. Excess intake enrichment decreased total lean mass increased nighttime...

10.1152/ajpheart.00297.2017 article EN AJP Heart and Circulatory Physiology 2017-10-06

Table S11 from Clinical Efficacy of ONC201 in H3K27M-Mutant Diffuse Midline Gliomas Is Driven by Disruption of Integrated Metabolic and Epigenetic Pathways

OPENALEX - Publications

Sriram Venneti Abed Rahman Kawakibi Sunjong Ji Sebastian M. Waszak Stefan R. Sweha and 79 more

Volcano plot of differentially expressed genes in DIPG007 cells treated with ONC201 versus vehicle.

10.1158/2159-8290.28436515 preprint EN cc-by 2025-02-18

Table S3 from Clinical Efficacy of ONC201 in H3K27M-Mutant Diffuse Midline Gliomas Is Driven by Disruption of Integrated Metabolic and Epigenetic Pathways

OPENALEX - Publications

Sriram Venneti Abed Rahman Kawakibi Sunjong Ji Sebastian M. Waszak Stefan R. Sweha and 79 more

Individual cases from historical control datasets.

10.1158/2159-8290.28436494 preprint EN cc-by 2025-02-18

Table S8 from Clinical Efficacy of ONC201 in H3K27M-Mutant Diffuse Midline Gliomas Is Driven by Disruption of Integrated Metabolic and Epigenetic Pathways

OPENALEX - Publications

Sriram Venneti Abed Rahman Kawakibi Sunjong Ji Sebastian M. Waszak Stefan R. Sweha and 79 more

Expression values, Spearman’s correlation coefficient, and GSEA of genes associated with positive or negative radiographic response to ONC201 treatment.

10.1158/2159-8290.28436479 preprint EN cc-by 2025-02-18

Table S13 from Clinical Efficacy of ONC201 in H3K27M-Mutant Diffuse Midline Gliomas Is Driven by Disruption of Integrated Metabolic and Epigenetic Pathways

OPENALEX - Publications

Sriram Venneti Abed Rahman Kawakibi Sunjong Ji Sebastian M. Waszak Stefan R. Sweha and 79 more

GSEA analysis of genes with significantly lower chromatin accessibility at promoters and enhancers reduced gene expression in DIPG007 cells treated ONC201 versus vehicle.

10.1158/2159-8290.28436509 preprint EN cc-by 2025-02-18

Table S10 from Clinical Efficacy of ONC201 in H3K27M-Mutant Diffuse Midline Gliomas Is Driven by Disruption of Integrated Metabolic and Epigenetic Pathways

OPENALEX - Publications

Sriram Venneti Abed Rahman Kawakibi Sunjong Ji Sebastian M. Waszak Stefan R. Sweha and 79 more

Upregulated and downregulated metabolites in DIPG007 cells treated with ONC201 versus vehicle.

10.1158/2159-8290.28436518 preprint EN cc-by 2025-02-18

Table S15 from Clinical Efficacy of ONC201 in H3K27M-Mutant Diffuse Midline Gliomas Is Driven by Disruption of Integrated Metabolic and Epigenetic Pathways

OPENALEX - Publications

Sriram Venneti Abed Rahman Kawakibi Sunjong Ji Sebastian M. Waszak Stefan R. Sweha and 79 more

GSEA analysis of genes with significantly increased H3K27me3 in ONC201-treated versus untreated patients.

10.1158/2159-8290.28436503 preprint EN cc-by 2025-02-18

Supplementary Data S1 from Clinical Efficacy of ONC201 in H3K27M-Mutant Diffuse Midline Gliomas Is Driven by Disruption of Integrated Metabolic and Epigenetic Pathways

OPENALEX - Publications

Sriram Venneti Abed Rahman Kawakibi Sunjong Ji Sebastian M. Waszak Stefan R. Sweha and 79 more

Protocol for NCT03416530, ONC201-014: ONC201 in Newly Diagnosed Diffuse Intrinsic Pontine Glioma and Recurrent/Refractory Pediatric H3K27M Gliomas.

10.1158/2159-8290.28436530 preprint EN cc-by 2025-02-18

Table S16 from Clinical Efficacy of ONC201 in H3K27M-Mutant Diffuse Midline Gliomas Is Driven by Disruption of Integrated Metabolic and Epigenetic Pathways

OPENALEX - Publications

Sriram Venneti Abed Rahman Kawakibi Sunjong Ji Sebastian M. Waszak Stefan R. Sweha and 79 more

ONC201 dosage chart for patients younger than 18 years of age.

10.1158/2159-8290.28436500 preprint EN cc-by 2025-02-18

Table S9 from Clinical Efficacy of ONC201 in H3K27M-Mutant Diffuse Midline Gliomas Is Driven by Disruption of Integrated Metabolic and Epigenetic Pathways

OPENALEX - Publications

Sriram Venneti Abed Rahman Kawakibi Sunjong Ji Sebastian M. Waszak Stefan R. Sweha and 79 more

Upregulated and downregulated genes in DIPG007 cells treated with ONC201 versus vehicle.

10.1158/2159-8290.28436476 preprint EN cc-by 2025-02-18

Table S6 from Clinical Efficacy of ONC201 in H3K27M-Mutant Diffuse Midline Gliomas Is Driven by Disruption of Integrated Metabolic and Epigenetic Pathways

OPENALEX - Publications

Sriram Venneti Abed Rahman Kawakibi Sunjong Ji Sebastian M. Waszak Stefan R. Sweha and 79 more

Radiographic response versus gene expression Spearman's correlation coefficient for all protein-coding genes.

10.1158/2159-8290.28436485 preprint EN cc-by 2025-02-18

Supplementary Data S2 from Clinical Efficacy of ONC201 in H3K27M-Mutant Diffuse Midline Gliomas Is Driven by Disruption of Integrated Metabolic and Epigenetic Pathways

OPENALEX - Publications

Sriram Venneti Abed Rahman Kawakibi Sunjong Ji Sebastian M. Waszak Stefan R. Sweha and 79 more

Protocol for NCT03134131, ONC201-018: Expanded Access to ONC201 Patients with H3K27M-mutant and/or Midline High Grade Gliomas.

10.1158/2159-8290.28436527 preprint EN cc-by 2025-02-18

Table S4 from Clinical Efficacy of ONC201 in H3K27M-Mutant Diffuse Midline Gliomas Is Driven by Disruption of Integrated Metabolic and Epigenetic Pathways

OPENALEX - Publications

Sriram Venneti Abed Rahman Kawakibi Sunjong Ji Sebastian M. Waszak Stefan R. Sweha and 79 more

Summary of historical control datasets.

10.1158/2159-8290.28436491 preprint EN cc-by 2025-02-18

Table S5 from Clinical Efficacy of ONC201 in H3K27M-Mutant Diffuse Midline Gliomas Is Driven by Disruption of Integrated Metabolic and Epigenetic Pathways

OPENALEX - Publications

Sriram Venneti Abed Rahman Kawakibi Sunjong Ji Sebastian M. Waszak Stefan R. Sweha and 79 more

VST-transformed gene expression values for all samples and protein-coding genes.

10.1158/2159-8290.28436488 preprint EN cc-by 2025-02-18

Table S7 from Clinical Efficacy of ONC201 in H3K27M-Mutant Diffuse Midline Gliomas Is Driven by Disruption of Integrated Metabolic and Epigenetic Pathways

OPENALEX - Publications

Sriram Venneti Abed Rahman Kawakibi Sunjong Ji Sebastian M. Waszak Stefan R. Sweha and 79 more

GSEA of genes associated with positive or negative correlation radiographic response to ONC201 treatment.

10.1158/2159-8290.28436482 preprint EN cc-by 2025-02-18

Table S1 from Clinical Efficacy of ONC201 in H3K27M-Mutant Diffuse Midline Gliomas Is Driven by Disruption of Integrated Metabolic and Epigenetic Pathways

OPENALEX - Publications

Sriram Venneti Abed Rahman Kawakibi Sunjong Ji Sebastian M. Waszak Stefan R. Sweha and 79 more

Baseline characteristics of ONC201-treated H3K27M-DMG patients included in analysis.

10.1158/2159-8290.28436521 preprint EN cc-by 2025-02-18

Supplementary Figures 1-15 from Clinical Efficacy of ONC201 in H3K27M-Mutant Diffuse Midline Gliomas Is Driven by Disruption of Integrated Metabolic and Epigenetic Pathways

OPENALEX - Publications

Sriram Venneti Abed Rahman Kawakibi Sunjong Ji Sebastian M. Waszak Stefan R. Sweha and 79 more

Contains supplementary data and table titles as well figures with associated legends.Fig. S1. Selection method for planned efficacy analysis of ONC201 in patients H3K27MDMG.Fig. S2. Progression-free survival from diagnosis trial non-recurrent H3K27MDMG treated ONC201.Fig. S3. Swimmers’ plot response by recurrence status, tumor location, trial.Fig. S4. is independent TP53 mutation status chromosomal instability.Fig. S5. Cox proportional hazard regression to assess the effect after...

10.1158/2159-8290.28436524 preprint EN cc-by 2025-02-18

Table S14 from Clinical Efficacy of ONC201 in H3K27M-Mutant Diffuse Midline Gliomas Is Driven by Disruption of Integrated Metabolic and Epigenetic Pathways

OPENALEX - Publications

Sriram Venneti Abed Rahman Kawakibi Sunjong Ji Sebastian M. Waszak Stefan R. Sweha and 79 more

GSEA analysis of genes with significantly lower H3K27ac at promoters and enhancers reduced gene expression in DIPG007 cells treated ONC201 versus vehicle.

10.1158/2159-8290.28436506 preprint EN cc-by 2025-02-18

Table S12 from Clinical Efficacy of ONC201 in H3K27M-Mutant Diffuse Midline Gliomas Is Driven by Disruption of Integrated Metabolic and Epigenetic Pathways

OPENALEX - Publications

Sriram Venneti Abed Rahman Kawakibi Sunjong Ji Sebastian M. Waszak Stefan R. Sweha and 79 more

Results of pathway impact analysis after performing integrated RNA-seq and metabolomics using MetaboAnalyst.

10.1158/2159-8290.28436512 preprint EN cc-by 2025-02-18

Table S2 from Clinical Efficacy of ONC201 in H3K27M-Mutant Diffuse Midline Gliomas Is Driven by Disruption of Integrated Metabolic and Epigenetic Pathways

OPENALEX - Publications

Sriram Venneti Abed Rahman Kawakibi Sunjong Ji Sebastian M. Waszak Stefan R. Sweha and 79 more

Individual patients with H3K27M-mutant DMG treated ONC201.

10.1158/2159-8290.28436497 preprint EN cc-by 2025-02-18

HUWE1 stimulates mTORC1 activity by enhancing Rheb interaction with mTORC1 and supports de novo pyrimidine synthesis

OPENALEX - Publications

Takayuki Ikeda Sungki Hong Shota Yoshida Abhiram Kunamneni Swayam Prakash Srivastava and 15 more

mTORC1 is a central regulator of cell growth that directly activated by the small GTPase Rheb on lysosomal membrane in response to factors. We recently reported polyubiquitinated facilitates its interaction with mTORC1, leading activation. However, molecular mechanisms underlying ubiquitination and for activation are not fully understood. In this study, we demonstrate HUWE1, an E3 ubiquitin ligase, preferentially interacts ubiquitinated essential between mTOR, as well Additionally, HUWE1...

10.1101/2025.04.22.650033 preprint EN cc-by-nc-nd bioRxiv (Cold Spring Harbor Laboratory) 2025-04-23

Table S16 from Clinical efficacy of ONC201 in H3K27M-mutant diffuse midline gliomas is driven by disruption of integrated metabolic and epigenetic pathways

OPENALEX - Publications

Sriram Venneti Abed Rahman Kawakibi Sunjong Ji Sebastian M. Waszak Stefan R. Sweha and 79 more

ONC201 dosage chart for patients younger than 18 years of age.

10.1158/2159-8290.27026252.v1 preprint EN 2024-09-16

Table S2 from Clinical efficacy of ONC201 in H3K27M-mutant diffuse midline gliomas is driven by disruption of integrated metabolic and epigenetic pathways

OPENALEX - Publications

Sriram Venneti Abed Rahman Kawakibi Sunjong Ji Sebastian M. Waszak Stefan R. Sweha and 79 more

Individual patients with H3K27M-mutant DMG treated ONC201.

10.1158/2159-8290.27026249 preprint EN 2024-09-16