Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

An acquired vulnerability of drug resistant melanoma with therapeutic potential

ABSTRACT: An acquired vulnerability of drug resistant melanoma with therapeutic potential

PROVIDER: PRJNA436000 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR6757700.fastq.gz	Fastqsanger.gz
	SRR6757710.fastq.gz	Fastqsanger.gz
	SRR6757701.fastq.gz	Fastqsanger.gz
	SRR6757711.fastq.gz	Fastqsanger.gz
	SRR6757702.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 27

Similar Datasets

An acquired vulnerability of drug resistant melanoma with therapeutic potential

Project description:This SuperSeries is composed of the SubSeries listed below.

2018-04-18 | GSE111141 | GEO

The AhR-SRC axis as a therapeutic vulnerability in BRAFi-resistant melanoma

Project description:The AhR-SRC axis as a therapeutic vulnerability in BRAFi-resistant melanoma

| PRJNA701428 | ENA

Vulnerability of drug-resistant EML4-ALK rearranged lung cancer to transcriptional inhibition

Project description:A subset of lung adenocarcinomas is driven by the EML4-ALK translocation. Despite excellent initial responses in patients, acquired resistance to ALK inhibitors occurs. Exploring these mechanisms of resistance, we found that EML4-ALK cells resistant to ALK inhibitors are remarkably sensitive to THZ1, alvocidib or dinaciclib. These compounds robustly induce apoptosis through transcriptional inhibition and downregulation of anti-apoptotic genes. In conclusion, this study shows that THZ1, alvocidib or dinaciclib could be a therapeutic option for a subset of patients with acquired resistance to first, second and third-generation ALK inhibitors.

2019-12-15 | E-MTAB-8563 | biostudies-arrayexpress

Vulnerability of drug-resistant EML4-ALK rearranged lung cancer to transcriptional inhibition

2019-12-22 | E-MTAB-8590 | biostudies-arrayexpress

Targeting CDK4/6 Represents a Therapeutic Vulnerability in Acquired BRAF/MEK Inhibitor-Resistant Melanoma.

Project description:There is a clear need to identify targetable drivers of resistance and potential biomarkers for salvage therapy for patients with melanoma refractory to the combination of BRAF and MEK inhibition. In this study, we performed whole-exome sequencing on BRAF-V600E-mutant melanoma patient tumors refractory to the combination of BRAF/MEK inhibition and identified acquired oncogenic mutations in NRAS and loss of the tumor suppressor gene CDKN2A We hypothesized the acquired resistance mechanisms to BRAF/MEK inhibition were reactivation of the MAPK pathway and activation of the cell-cycle pathway, which can both be targeted pharmacologically with the combination of a MEK inhibitor (trametinib) and a CDK4/6 inhibitor (palbociclib). In vivo, we found that combination of CDK4/6 and MEK inhibition significantly decreased tumor growth in two BRAF/MEK inhibitor-resistant patient-derived xenograft models. In vitro, we observed that the combination of CDK4/6 and MEK inhibition resulted in synergy and significantly reduced cellular growth, promoted cell-cycle arrest, and effectively inhibited downstream signaling of MAPK and cell-cycle pathways in BRAF inhibitor-resistant cell lines. Knockdown of CDKN2A in BRAF inhibitor-resistant cells increased sensitivity to CDK4/6 inhibition alone and in combination with MEK inhibition. A key implication of our study is that the combination of CDK4/6 and MEK inhibitors overcomes acquired resistance to BRAF/MEK inhibitors, and loss of CDKN2A may represent a biomarker of response to the combination. Inhibition of the cell-cycle and MAPK pathway represents a promising strategy for patients with metastatic melanoma who are refractory to BRAF/MEK inhibitor therapy.

| S-EPMC9768695 | biostudies-literature

MITF Expression Predicts Therapeutic Vulnerability to p300 Inhibition in Human Melanoma

Project description:MITF Expression Predicts Therapeutic Vulnerability to p300 Inhibition in Human Melanoma

| PRJNA528651 | ENA

Proteomic and phosphoproteomics profiling depict drug addiction mechanisms in BRAFi-resistant melanoma

Project description:Acquired resistance to MAPK inhibitors limits the clinical efficacy in melanoma treatment. We and others have recently shown that BRAF inhibitors (BRAFi)-resistant melanoma cells can develop a dependency on the therapeutic drugs to which they have acquired resistance, creating a vulnerability for these cells that can potentially be exploited in cancer treatment. In drug addicted melanoma cells, it was shown that this induction of cell death was preceded by a specific ERK2-dependent phenotype switch, however, the underlying molecular mechanisms are largely lacking. To increase the molecular understanding of this drug dependency, we applied a mass spectrometry-based proteomic approach on BRAFi-resistant BRAFMUT 451Lu cells, in which ERK1, ERK2 and JUNB were silenced separately using CRISPR–Cas9. Inactivation of ERK2 and, to a lesser extent, JUNB prevents drug addiction in these melanoma cell while, conversely, knock out of ERK1 fails to reverse this phenotype, showing a response similar to control cells. Our analysis reveals that ERK2 and JUNB share comparable proteome responses dominated by reactivation of cell division. Importantly, we find that EMT activation in drug addicted melanoma cells upon drug withdrawal is affected by silencing ERK2 but not ERK1. Moreover, transcription factor (regulator) enrichment shows that PIR acts as an effector of ERK2 and phosphoproteome analysis reveals that silencing of ERK2 but not ERK1 leads to amplification of GSK3 kinase activity. Our results depict possible mechanisms of drug addiction in melanoma, which may provide a guide for strategies in drug-resistant melanoma.

2022-02-17 | PXD026557 | Pride

Targeting Electron Transport Chain Confers Therapeutic Vulnerability in Castration-Resistant Prostate Cancer

Project description:Targeting Electron Transport Chain Confers Therapeutic Vulnerability in Castration-Resistant Prostate Cancer

| PRJNA853056 | ENA

CDK7 is a novel therapeutic vulnerability in Fibrolamellar cancer

Project description:CDK7 is a novel therapeutic vulnerability in Fibrolamellar cancer

| PRJNA971878 | ENA

The AhR-SRC axis as a therapeutic vulnerability in BRAFi-resistant melanoma.

Project description:The nongenetic mechanisms required to control tumor phenotypic plasticity and shape drug-resistance remain unclear. We show here that the Aryl hydrocarbon Receptor (AhR) transcription factor directly regulates the gene expression program associated with the acquisition of resistance to BRAFi in melanoma. In addition, we show in melanoma cells that canonical activation of AhR mediates the activation of the SRC pathway and promotes the acquisition of an invasive and aggressive resistant phenotype to front-line BRAF inhibitor treatment in melanoma. This nongenetic reprogramming identifies a clinically-compatible approach to reverse BRAFi resistance in melanoma. Using a preclinical BRAFi resistant PDX melanoma model, we demonstrate that SRC inhibition with dasatinib significantly re-sensitizes melanoma cells to BRAFi. Together we identify the AhR/SRC axis as a new therapeutic vulnerability to trigger resistance and warrant the introduction of SRC inhibitors during the course of the treatment in combination with front-line therapeutics to delay BRAFi-resistance.

| S-SCDT-10_15252-EMMM_202215677 | biostudies-other

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data