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View article: Synergistic inhibition of CHK1 and MUS81 to combat replication stress resistance in high-risk neuroblastoma
Synergistic inhibition of CHK1 and MUS81 to combat replication stress resistance in high-risk neuroblastoma Open
High-risk neuroblastoma is a pediatric tumor that originates from immature sympathetic neuroblasts and is characterized by a low mutational burden. Nevertheless, it frequently presents with highly recurrent chromosomal imbalances, includin…
View article: Dual lipid modulation overcomes ferroptosis resistance in high-risk neuroblastoma
Dual lipid modulation overcomes ferroptosis resistance in high-risk neuroblastoma Open
Ferroptosis—an iron-dependent form of cell death triggered by phospholipid peroxidation—has emerged as a promising therapeutic avenue in cancer treatment. Although neuroblastoma (NB) has been identified as a ferroptosis susceptible cancer,…
View article: Second-Generation AURKA-Targeting PROTACs: Structural Optimization toward in Vivo Degradation in Neuroblastoma
Second-Generation AURKA-Targeting PROTACs: Structural Optimization toward in Vivo Degradation in Neuroblastoma Open
Aurora kinase A (AURKA) is an established oncogenic factor and therapeutic target in neuroblastoma due to its roles in mitosis and stability of the MYCN protein. We previously identified SK2188 as a highly potent, selective, and fast-actin…
View article: Targeting replication stress in neuroblastoma by exploiting the synergistic potential of second generation RRM2 and CHK1 inhibitors
Targeting replication stress in neuroblastoma by exploiting the synergistic potential of second generation RRM2 and CHK1 inhibitors Open
Tumor cells often cope with elevated levels of replication stress (RS) causing increased dependency on ATR-CHK1 signalling. We previously presented RRM2, the regulatory component of the ribonucleotide reductase (RNR) enzyme, as novel depen…
View article: TPX2 is a downstream target of the eIF4A controlled translational program in neuroblastoma
TPX2 is a downstream target of the eIF4A controlled translational program in neuroblastoma Open
Current therapies for neuroblastoma are often ineffective and survivors suffer from severe long-term therapy related side-effects, underscoring the need for identification of novel drugging strategies. We performed an in-depth evaluation o…
View article: A dual role for PSIP1/LEDGF in T cell acute lymphoblastic leukemia
A dual role for PSIP1/LEDGF in T cell acute lymphoblastic leukemia Open
T cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy. Current intensified therapeutic protocols coincide with severe side effects, and no salvage therapy is available for primary therapy-resistant or relaps…
View article: 5’UTR translational inhibition of neuroblastoma dependency factors using the CR-1-31-B rocaglate
5’UTR translational inhibition of neuroblastoma dependency factors using the CR-1-31-B rocaglate Open
Summary Current therapies for neuroblastoma are often ineffective and survivors suffer from severe long-term therapy related side-effects, underscoring the need for identification of novel drugging strategies. We performed an in-depth eval…
View article: DNA repair and replicative stress addiction in neuroblastoma
DNA repair and replicative stress addiction in neuroblastoma Open
Neuroblastoma (NB) is a pediatric tumor of the sympathetic nervous system. Survival remains poor for the almost 40 % of patients with high-risk NB. Targeted therapy options for high-risk NB are limited and single compound strategies often …
View article: HTSplotter: An end-to-end data processing, analysis and visualisation tool for chemical and genetic in vitro perturbation screening
HTSplotter: An end-to-end data processing, analysis and visualisation tool for chemical and genetic in vitro perturbation screening Open
In biomedical research, high-throughput screening is often applied as it comes with automatization, higher-efficiency, and more and faster results. High-throughput screening experiments encompass drug, drug combination, genetic perturbagen…
View article: RUVBL1 and RUVBL2 as novel druggable DNA Damage Response regulators in the N-Myc regulatory network in neuroblastoma
RUVBL1 and RUVBL2 as novel druggable DNA Damage Response regulators in the N-Myc regulatory network in neuroblastoma Open
High-risk neuroblastoma (NB) accounts for about 50% of all cases. These tumours are characterized by MYCN amplification and high MYC gene expression and patients have a high relapse rate despite intensive therapies, hence the need for safe…
View article: Post‐operative minimal residual disease models to study metastatic relapse in soft‐tissue sarcoma patient‐derived xenografts
Post‐operative minimal residual disease models to study metastatic relapse in soft‐tissue sarcoma patient‐derived xenografts Open
Soft-tissue sarcomas (STS) are rare, heterogeneous cancers comprising 1% of adult and 15% of paediatric malignancies. Despite optimal treatment, 50%−80% of patients metastasize, even when they attain a status of minimal residual disease (M…
View article: The fork restart factor PHF6 interacts with RRM2 and binds to H3K56ac marked nascent DNA
The fork restart factor PHF6 interacts with RRM2 and binds to H3K56ac marked nascent DNA Open
The PHF6 protein is a presumed chromatin reader implicated in disease through germline loss-of-function mutations causing cognitive disability syndromes and somatic mutations are predominantly observed in acute T-cell leukemia. Previous re…
View article: Exploration of neuroblastoma xenograft models for tumor extracellular RNA profiling in murine blood plasma
Exploration of neuroblastoma xenograft models for tumor extracellular RNA profiling in murine blood plasma Open
Background: Minimally invasive liquid biopsies are becoming increasingly important in the diagnosis and treatment follow-up of cancer patients, including children with neuroblastoma. Such biopsies contain various biomarker analytes, includ…
View article: TPX2 as Key Downstream Target of the eIF4A Controlled Translational Program in MYCN Driven Neuroblastoma
TPX2 as Key Downstream Target of the eIF4A Controlled Translational Program in MYCN Driven Neuroblastoma Open
View article: RUVBL1 and RUVBL2 as Novel Druggable DNA Damage Response Regulators in the N-Myc Regulatory Network in Neuroblastoma
RUVBL1 and RUVBL2 as Novel Druggable DNA Damage Response Regulators in the N-Myc Regulatory Network in Neuroblastoma Open
View article: Targeted AURKA degradation: Towards new therapeutic agents for neuroblastoma
Targeted AURKA degradation: Towards new therapeutic agents for neuroblastoma Open
View article: Whole transcriptome profiling of liquid biopsies from tumour xenografted mouse models enables specific monitoring of tumour-derived extracellular RNA
Whole transcriptome profiling of liquid biopsies from tumour xenografted mouse models enables specific monitoring of tumour-derived extracellular RNA Open
While cell-free DNA (cfDNA) is widely being investigated, free circulating RNA (extracellular RNA, exRNA) has the potential to improve cancer therapy response monitoring and detection due to its dynamic nature. However, it remains unclear …
View article: Targeted AURKA degradation: towards new therapeutic agents for neuroblastoma
Targeted AURKA degradation: towards new therapeutic agents for neuroblastoma Open
Aurora kinase A (AURKA) is a well-established target in neuroblastoma (NB) due to its catalytic functions during mitosis and due to stabilisation of the key oncoprotein MYCN. We report a small structure-activity relationship (SAR) study of…
View article: RRM2 enhances MYCN-driven neuroblastoma formation and acts as a synergistic target with CHK1 inhibition
RRM2 enhances MYCN-driven neuroblastoma formation and acts as a synergistic target with CHK1 inhibition Open
High-risk neuroblastoma, a pediatric tumor originating from the sympathetic nervous system, has a low mutation load but highly recurrent somatic DNA copy number variants. Previously, segmental gains and/or amplifications allowed identifica…
View article: From DNA Copy Number Gains and Tumor Dependencies to Novel Therapeutic Targets for High-Risk Neuroblastoma
From DNA Copy Number Gains and Tumor Dependencies to Novel Therapeutic Targets for High-Risk Neuroblastoma Open
Neuroblastoma is a pediatric tumor arising from the sympatho-adrenal lineage and a worldwide leading cause of childhood cancer-related deaths. About half of high-risk patients die from the disease while survivors suffer from multiple thera…
View article: MEIS2 Is an Adrenergic Core Regulatory Transcription Factor Involved in Early Initiation of TH-MYCN-Driven Neuroblastoma Formation
MEIS2 Is an Adrenergic Core Regulatory Transcription Factor Involved in Early Initiation of TH-MYCN-Driven Neuroblastoma Formation Open
Roughly half of all high-risk neuroblastoma patients present with MYCN amplification. The molecular consequences of MYCN overexpression in this aggressive pediatric tumor have been studied for decades, but thus far, our understanding of th…
View article: HTSplotter: an end-to-end data processing, analysis and visualisation tool for chemical and genetic <i>in vitro</i> perturbation screening
HTSplotter: an end-to-end data processing, analysis and visualisation tool for chemical and genetic <i>in vitro</i> perturbation screening Open
In biomedical research, high-throughput screening is often applied as it comes with automatization, higher-efficiency, and more and faster results. High-throughput screening experiments encompass drug, drug combination, genetic perturbagen…
View article: MYCN-induced nucleolar stress drives an early senescence-like transcriptional program in hTERT-immortalized RPE cells
MYCN-induced nucleolar stress drives an early senescence-like transcriptional program in hTERT-immortalized RPE cells Open
MYCN is an oncogenic driver in neural crest-derived neuroblastoma and medulloblastoma. To better understand the early effects of MYCN activation in a neural-crest lineage context, we profiled the transcriptome of immortalized human retina …
View article: MYCN-induced nucleolar stress drives an early senescence-like transcriptional program in hTERT-immortalized RPE cells
MYCN-induced nucleolar stress drives an early senescence-like transcriptional program in hTERT-immortalized RPE cells Open
MYCN is an oncogenic driver in neural crest-derived neuroblastoma and medulloblastoma. To better understand the early effects of MYCN activation in a neural-crest lineage context, we profiled the transcriptome of immortalized human retina …
View article: Large-scale circular RNA deregulation in T-ALL: unlocking unique ectopic expression of molecular subtypes
Large-scale circular RNA deregulation in T-ALL: unlocking unique ectopic expression of molecular subtypes Open
Circular RNAs (circRNAs) are stable RNA molecules that can drive cancer through interactions with microRNAs and proteins and by the expression of circRNA encoded peptides. The aim of the study was to define the circRNA landscape and potent…
View article: RRM2 is a target for synthetic lethal interactions with replication stress checkpoint addiction in high-risk neuroblastoma
RRM2 is a target for synthetic lethal interactions with replication stress checkpoint addiction in high-risk neuroblastoma Open
Summary Neuroblastoma is a pediatric tumor originating from the sympathetic nervous system responsible for 10-15 percent of all childhood cancer deaths. Half of all neuroblastoma patients present with high-risk disease at diagnosis. Despit…
View article: Comprehensive benchmarking of single cell RNA sequencing technologies for characterizing cellular perturbation
Comprehensive benchmarking of single cell RNA sequencing technologies for characterizing cellular perturbation Open
Technological advances in transcriptome sequencing of single cells continues to provide an unprecedented view on tissue composition and cellular heterogeneity. While several studies have compared different single cell RNA-seq methods with …
View article: Recurrent chromosomal imbalances provide selective advantage to human embryonic stem cells under enhanced replicative stress conditions
Recurrent chromosomal imbalances provide selective advantage to human embryonic stem cells under enhanced replicative stress conditions Open
Human embryonic stem cells (hESCs) and embryonal tumors share a number of common features including a compromised G1/S checkpoint. Consequently, these rapidly dividing hESCs and cancer cells undergo elevated levels of replicative stress wh…
View article: PHF6 Expression Levels Impact Human Hematopoietic Stem Cell Differentiation
PHF6 Expression Levels Impact Human Hematopoietic Stem Cell Differentiation Open
Transcriptional control of hematopoiesis involves complex regulatory networks and functional perturbations in one of these components often results in malignancies. Loss-of-function mutations in PHF6, encoding a presumed epigenetic …
View article: A novel TLX1-driven T-ALL zebrafish model: comparative genomic analysis with other leukemia models
A novel TLX1-driven T-ALL zebrafish model: comparative genomic analysis with other leukemia models Open