Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Global profiling of cancer cell recovery from therapy-induced stress reveals druggable vulnerabilities

ABSTRACT: Global profiling of cancer cell recovery from therapy-induced stress reveals druggable vulnerabilities

PROVIDER: PRJNA665050 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR12694311_1.fastq.gz	Fastqsanger.gz
	SRR12694311_2.fastq.gz	Fastqsanger.gz
	SRR12694312_1.fastq.gz	Fastqsanger.gz
	SRR12694312_2.fastq.gz	Fastqsanger.gz
	SRR12694313_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 70

Similar Datasets

Global profiling of cancer cell recovery from therapy-induced stress reveals druggable vulnerabilities

Project description:Cancer cells survive therapy-induced stress, but how they resolve it is not clear. Using an integrated systems level approach we delineate the global mechanisms of cellular recovery from proteotoxic stress. Our findings in proteasome inhibitor-treated myeloma cells provide a layered chart of the protracted processes of stress resolution that encompass extensive metabolic changes. Tumour cells that have survived proteasome inhibition and are recovering from proteotoxic injuries are more vulnerable to certain insults than acutely stressed or unstressed cells. We identify mitochondria and the GCN2-driven cellular response to amino acid depletion as examples of recovery-associated vulnerabilities, and demonstrate that GCN2 is a bona fide target in transcriptional signature-defined subsets of solid cancers irrespective of prior proteasome inhibition. Thus, targeting multi-system vulnerabilities tied to cellular recovery from drug-induced stress has the potential to optimise cancer therapies.

2021-04-15 | GSE158387 | GEO

Whole genome CRISPRi screening identifies druggable vulnerabilities in drug-resistant Mycobacterium tuberculosis

Project description:<p>Tuberculosis (TB) remains a global health threat, aggravated by the emergence of drug-resistant strains. This study aims to identify genes and metabolic pathways with increased vulnerability in drug-resistant Mycobacterium tuberculosis strains compared to their drug-susceptible counterparts. Using CRISPR interference (CRISPRi), we screened for critical pathways unique or shared across resistant strains. The findings reveal potential therapeutic targets, offering new avenues for anti-TB drug development. This approach addresses the urgent need for effective treatments against drug-resistant TB and advances our understanding of its underlying resistance mechanisms. This work highlights how changes in the physiology of drug-resistant strains generate druggable vulnerabilities that can be exploited to improve clinical outcomes.</p>

2024-10-15 | MTBLS11277 | MetaboLights

RNA Terminal Uridylyl-Transferases Are Druggable Vulnerabilities in AML, but are Dispensable for Normal Hematopoiesis

Project description:RNA Terminal Uridylyl-Transferases Are Druggable Vulnerabilities in AML, but are Dispensable for Normal Hematopoiesis

| PRJNA1371002 | ENA

RNA Terminal Uridylyl-Transferases Are Druggable Vulnerabilities in AML, but are Dispensable for Normal Hematopoiesis

Project description:RNA Terminal Uridylyl-Transferases Are Druggable Vulnerabilities in AML, but are Dispensable for Normal Hematopoiesis

| PRJNA1447503 | ENA

RNA Terminal Uridylyl-Transferases Are Druggable Vulnerabilities in AML, but are Dispensable for Normal Hematopoiesis [SLAM-Seq]

Project description:RNA Terminal Uridylyl-Transferases Are Druggable Vulnerabilities in AML, but are Dispensable for Normal Hematopoiesis [SLAM-Seq]

| PRJNA1449483 | ENA

RNA Terminal Uridylyl-Transferases Are Druggable Vulnerabilities in AML, but are Dispensable for Normal Hematopoiesis [RNA-seq]

Project description:RNA Terminal Uridylyl-Transferases Are Druggable Vulnerabilities in AML, but are Dispensable for Normal Hematopoiesis [RNA-seq]

| PRJNA1450008 | ENA

RNA Terminal Uridylyl-Transferases Are Druggable Vulnerabilities in AML, but are Dispensable for Normal Hematopoiesis

Project description:Acute myeloid leukemia (AML) is an aggressive hematological malignancy arising from blood-forming hematopoietic stem and progenitor cells (HSPCs). Current therapies often fail to eradicate AML, therefore, identification of novel therapeutic targets is essential. Here, we reveal Terminal Uridylyl Transferase Enzymes 4 and 7 (TUT4/7) as druggable novel therapeutic targets whose genetic deletion in AML suppresses growth, induces apoptosis and improves the survival of in vivo mouse models. Use of a pre-clinical TUT4/7 inhibitor is cytotoxic to AML patient samples, dysregulates mevalonate pathway genes and synergizes with Venetoclax. AML therapies are often limited by hematopoietic toxicity. Remarkably, we find that although Tut4/7 deletion results in mild inflammatory activation throughout the hematopoietic system, this activation is largely permissive, and mice exhibit no overt pathology for at least one year. Thus, we reveal TUT4/7 as novel druggable therapeutic targets, whose inactivation compromises AML while sparing normal hematopoiesis.

2026-07-17 | GSE311841 | GEO

RNA Terminal Uridylyl-Transferases Are Druggable Vulnerabilities in AML, but are Dispensable for Normal Hematopoiesis

Project description:Acute myeloid leukemia (AML) is an aggressive hematological malignancy arising from hematopoietic stem and progenitor cells (HSPCs). Current treatments often fail to eradicate AML; therefore, new therapeutic strategies are essential. Here, we reveal that RNA Terminal-Uridylyl-Transferase-Enzymes 4 and 7 (TUT4/7) are druggable therapeutic targets, whose genetic deletion suppresses AML growth, induces apoptosis and improves the survival in leukemic mouse models. Notably, a pre-clinical TUT4/7 inhibitor promotes cell death in AML patient samples and synergizes with venetoclax. Mechanistically, TUT4/7 inactivation suppresses mevalonate pathway gene expression, compromising the cholesterol synthesis pathway. Current AML therapies often cause severe hematopoietic toxicity. Although Tut4/7 deletion results in inflammatory activation throughout the hematopoietic system, this is permissive to a normal lifespan and Tut4/7-deficiency does not compromise HSPC function. Together, these findings identify TUT4/7 as druggable targets, whose inactivation suppresses AML while sparing normal hematopoiesis. In combination with venetoclax this represents a promising therapeutic strategy.

2026-06-24 | GSE326857 | GEO

RNA Terminal Uridylyl-Transferases Are Druggable Vulnerabilities in AML, but are Dispensable for Normal Hematopoiesis

Project description:Acute myeloid leukemia (AML) is an aggressive hematological malignancy arising from hematopoietic stem and progenitor cells (HSPCs). Current treatments often fail to eradicate AML, therefore, new therapeutic strategies are essential. Here, we reveal that RNA Terminal-Uridylyl-Transferase-Enzymes 4 and 7 (TUT4/7) as novel druggable therapeutic targets, whose genetic deletion in AML suppresses growth, induces apoptosis and improves the survival of leukemic mice. Notably, a pre-clinical TUT4/7 inhibitor promotes cell death in AML patient samples and synergizes with Venetoclax. Mechanistically, TUT4/7 inactivation disrupts cellular metabolism and suppresses mevalonate pathway gene expression, compromising the prenylation and cholesterol synthesis pathways. Current AML therapies often cause severe hematopoietic toxicity. Although Tut4/7 deletion results in inflammatory activation throughout the hematopoietic system, this is permissive to a normal lifespan and Tut4/7-deficiency does not compromise HSPC function. Thus, we reveal TUT4/7 as druggable targets, whose inactivation suppresses AML while sparing normal hematopoiesis. In combination with Venetoclax this represents a novel and promising therapeutic strategy.

2026-06-24 | PXD077084 | Pride

Enhancer remodeling promotes resistance to epigenetic-targeted therapy and engenders tumor cell vulnerabilities

Project description:Enhancer remodeling promotes resistance to epigenetic-targeted therapy and engenders tumor cell vulnerabilities

| PRJNA421166 | ENA