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A personalized medicine approach identifies enasidenib as an efficient treatment for IDH2 mutant chondrosarcoma

ABSTRACT: A personalized medicine approach identifies enasidenib as an efficient treatment for IDH2 mutant chondrosarcoma

PROVIDER: PRJNA986927 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR24998838_1.fastq.gz	Fastqsanger.gz
	SRR24998838_2.fastq.gz	Fastqsanger.gz
	SRR24998839_1.fastq.gz	Fastqsanger.gz
	SRR24998839_2.fastq.gz	Fastqsanger.gz
	SRR24998840_1.fastq.gz	Fastqsanger.gz

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A personalized medicine approach identifies enasidenib as an efficient treatment for IDH2 mutant chondrosarcoma [MethArray_5days]

Project description:The heterogenous genomic nature of most sarcoma subtypes makes them especially indicated for personalized treatment approaches. Here, we developed a personalized medicine strategy based in the use of patient-derived cell lines as a drug-testing platform. Targeted sequencing of a panel of cancer-related genes in these models revealed the presence of IDH1 and IDH2 mutations in two chondrosarcomas. Mutant IDH (mIDH) enzymes produce the oncometabolite 2-HG which contributes to driving tumor growth. Thus, we treated several chondrosarcoma models with specific mIDH1/2 inhibitors. Among these treatments, only the mIDH2 inhibitor enasidenib was able to decrease 2-HG levels and to efficiently reduce the viability of mIDH2 chondrosarcoma cells. Importantly, oral administration of enasidenib in xenografted mice resulted in a complete abrogation of tumor growth. Enasidenib induced a profound remodeling of the transcriptomic landscape not associated to changes in the 5mC methylation levels and its anti-tumor effects were associated to the repression of proliferative pathways such as those controlled by E2F factors. Overall, this work provides the first preclinical evidence for the use of enasidenib to treat mIDH2 chondrosarcomas.

2024-03-12 | GSE261421 | GEO

A personalized medicine approach identifies enasidenib as an efficient treatment for IDH2 mutant chondrosarcoma [RNAseq_Enasidenib_L2975_SW1353]

2024-03-13 | GSE261434 | GEO

A personalized medicine approach identifies enasidenib as an efficient treatment for IDH2 mutant chondrosarcoma [MethArray_2days]

2024-03-11 | GSE235697 | GEO

A personalized medicine approach identifies enasidenib as an efficient treatment for IDH2 mutant chondrosarcoma [RNAseq_Enasidenib_T-CDS17#1]

2024-03-11 | GSE235605 | GEO

A personalized medicine approach identifies enasidenib as an efficient treatment for IDH2 mutant chondrosarcoma [RNAseq_Enasidenib_L2975_SW1353]

Project description:A personalized medicine approach identifies enasidenib as an efficient treatment for IDH2 mutant chondrosarcoma [RNAseq_Enasidenib_L2975_SW1353]

| PRJNA1086938 | ENA

A personalized medicine approach identifies enasidenib as an efficient treatment for IDH2 mutant chondrosarcoma [MethArray_2days]

Project description:A personalized medicine approach identifies enasidenib as an efficient treatment for IDH2 mutant chondrosarcoma [MethArray_2days]

| PRJNA986918 | ENA

A personalized medicine approach identifies enasidenib as an efficient treatment for IDH2 mutant chondrosarcoma [MethArray_5days]

Project description:A personalized medicine approach identifies enasidenib as an efficient treatment for IDH2 mutant chondrosarcoma [MethArray_5days]

| PRJNA1086915 | ENA

A personalized medicine approach identifies enasidenib as an efficient treatment for IDH2 mutant chondrosarcoma [RNAseq_Enasidenib_T-CDS17#1]

Project description:A personalized medicine approach identifies enasidenib as an efficient treatment for IDH2 mutant chondrosarcoma [RNAseq_Enasidenib_T-CDS17#1]

| PRJNA986541 | ENA

Whole exome sequencing analyses of human, IDH2-mutated, acute myeloid leukemia samples from patients before or during treatment with Enasidenib.

Project description:Mutations in isocitrate dehydrogenase 2 (IDH2) occur in many cancers including Acute Myeloid Leukemia (AML). In preclinical models mutant IDH2 causes partial hemopoietic differentiation arrest. Recently, we showed that single agent Enasidenib, a first-in-class, selective mutant IDH2 inhibitor, produces a 40% response in relapsed/refractory AML patients by promoting differentiation. Yet, the rate, extend and duration of the clinical benefits of Enasidenib vary from one patient to another. To investigate how the genetic mutational landscape, at baseline or at relapse, contributes in modulating response to Enasidenib, WES analyses on FACS-sorted blasts from baseline, best response and/or relapse samples from 16 Enasidenib-treated patients were performed. WES analyses were also performed on the CD3+ cells from the same patients, which may be used as germinal control samples.

2018-08-13 | E-MTAB-6299 | biostudies-arrayexpress

RNA sequencing of human, IDH2-mutated, acute myeloid leukemia samples from patients before or during treatment with Enasidenib

Project description:Mutations in isocitrate dehydrogenase 2 (IDH2) occur in many cancers including Acute Myeloid Leukemia (AML). Recently, we showed that single agent Enasidenib, a first-in-class, selective mutant IDH2 inhibitor, produces a 40% response in relapsed/refractory AML patients by promoting differentiation of leukaemic cells. In this current study, we describe two patients who responded to Enasidenib treatment but subsequently relapsed with an IDH2-mutant subclone which had acquired mutations in DHX15 and DDX1 genes. These genes have putative functions in regulating splicing. We have studied the alternative splicing events using RNASeq in the sample pre-relapse (before acquisition of DHX15 and DDX1 mutations) and at relapse (after acquisition of DHX15 and DDX1 mutations).

2018-08-08 | E-MTAB-6660 | biostudies-arrayexpress

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