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Enhanced efficacy of aurora kinase inhibitors in G2/M checkpoint deficient TP53 mutant uterine carcinomas is linked to the summation of LKB1-AKT-p53 interactions

ABSTRACT: Enhanced efficacy of aurora kinase inhibitors in G2/M checkpoint deficient TP53 mutant uterine carcinomas is linked to the summation of LKB1-AKT-p53 interactions

PROVIDER: PRJNA719832 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR14146000_1.fastq.gz	Fastqsanger.gz
	SRR14146000_2.fastq.gz	Fastqsanger.gz
	SRR14146001_1.fastq.gz	Fastqsanger.gz
	SRR14146001_2.fastq.gz	Fastqsanger.gz
	SRR14146002_1.fastq.gz	Fastqsanger.gz

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Enhanced efficacy of aurora kinase inhibitors in G2/M checkpoint deficient TP53 mutant uterine carcinomas is linked to the summation of LKB1-AKT-p53 interactions [WGS]

Project description:Enhanced efficacy of aurora kinase inhibitors in G2/M checkpoint deficient TP53 mutant uterine carcinomas is linked to the summation of LKB1-AKT-p53 interactions [WGS]

| PRJNA719836 | ENA

Enhanced efficacy of aurora kinase inhibitors in G2/M checkpoint deficient TP53 mutant uterine carcinomas is linked to the summation of LKB1-AKT-p53 interactions [RNA-seq]

Project description:Enhanced efficacy of aurora kinase inhibitors in G2/M checkpoint deficient TP53 mutant uterine carcinomas is linked to the summation of LKB1-AKT-p53 interactions [RNA-seq]

| PRJNA719834 | ENA

Enhanced efficacy of aurora kinase inhibitors in G2/M checkpoint deficient TP53 mutant uterine carcinomas is linked to the summation of LKB1-AKT-p53 interactions [exome-seq]

Project description:Enhanced efficacy of aurora kinase inhibitors in G2/M checkpoint deficient TP53 mutant uterine carcinomas is linked to the summation of LKB1-AKT-p53 interactions [exome-seq]

| PRJNA719835 | ENA

Enhanced Efficacy of Aurora Kinase Inhibitors in G2/M Checkpoint Deficient TP53 Mutant Uterine Carcinomas Is Linked to the Summation of LKB1-AKT-p53 Interactions.

Project description:Uterine carcinoma (UC) is the most common gynecologic malignancy in the United States. TP53 mutant UCs cause a disproportionate number of deaths due to limited therapies for these tumors and the lack of mechanistic understanding of their fundamental vulnerabilities. Here we sought to understand the functional and therapeutic relevance of TP53 mutations in UC. We functionally profiled targetable TP53 dependent DNA damage repair and cell cycle control pathways in a panel of TP53 mutant UC cell lines and patient-derived organoids. There were no consistent defects in DNA damage repair pathways. Rather, most models demonstrated dependence on defective G2/M cell cycle checkpoints and subsequent upregulation of Aurora kinase-LKB1-p53-AKT signaling in the setting of baseline mitotic defects. This combination makes them sensitive to Aurora kinase inhibition. Resistant lines demonstrated an intact G2/M checkpoint, and combining Aurora kinase and WEE1 inhibitors, which then push these cells through mitosis with Aurora kinase inhibitor-induced spindle defects, led to apoptosis in these cases. Overall, this work presents Aurora kinase inhibitors alone or in combination with WEE1 inhibitors as relevant mechanism driven therapies for TP53 mutant UCs. Context specific functional assessment of the G2/M checkpoint may serve as a biomarker in identifying Aurora kinase inhibitor sensitive tumors.

| S-EPMC8125555 | biostudies-literature

Enhanced efficacy of aurora kinase inhibitors in G2/M checkpoint deficient TP53 mutant uterine carcinomas is linked to the summation of LKB1-AKT-p53 interactions

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

2021-05-07 | GSE171516 | GEO

Enhanced efficacy of aurora kinase inhibitors in G2/M checkpoint deficient TP53 mutant uterine carcinomas is linked to the summation of LKB1-AKT-p53 interactions [WGS]

Project description:We report bulk RNA sequencing, low pass whole genome sequencing, and targeted exome sequencing data of six uterine cancer organoids and show how specific molecular defects in these organoids make them sensitive to cell cycle targeting therapies.

2021-05-08 | GSE171515 | GEO

Enhanced efficacy of aurora kinase inhibitors in G2/M checkpoint deficient TP53 mutant uterine carcinomas is linked to the summation of LKB1-AKT-p53 interactions [exome-seq]

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Enhanced efficacy of aurora kinase inhibitors in G2/M checkpoint deficient TP53 mutant uterine carcinomas is linked to the summation of LKB1-AKT-p53 interactions [RNA-seq]

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