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An epigenetic vulnerability in PI3K/AKT inhibition resistant cancers is targetable by both bromodomain and HDAC inhibitors

ABSTRACT: An epigenetic vulnerability in PI3K/AKT inhibition resistant cancers is targetable by both bromodomain and HDAC inhibitors

PROVIDER: PRJNA614914 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR11403000_1.fastq.gz	Fastqsanger.gz
	SRR11403000_2.fastq.gz	Fastqsanger.gz
	SRR11403001_1.fastq.gz	Fastqsanger.gz
	SRR11403001_2.fastq.gz	Fastqsanger.gz
	SRR11403002_1.fastq.gz	Fastqsanger.gz

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An epigenetic vulnerability in PI3K/AKT inhibition resistant cancers is targetable by both bromodomain and HDAC inhibitors

Project description:Acquisition of resistance to PI3K/AKT-targeted monotherapy regardless of cancer types implies the existence of common mechanisms. Here we demonstrate that while causing glycolysis crisis, acetyl-CoA shortage and global decrease of histone acetylation, PI3K/AKT inhibitors induce drug resistance by selectively augmenting CBP/p300, H3K27 acetylation and BRD4 binding at genomic loci of a subset of growth factor and receptor (GF/R) genes. BRD4 occupation at these loci and drug resistant cell growth are vulnerable to both bromodomain and HDAC inhibitors. Little or none occupation of HDACs at the GF/R gene loci underscores the paradox that cells respond equivalently to the two classes of inhibitors with opposite modes of action. Targeting this unique epigenetic vulnerability offers a general solution to overcome PI3K/AKT inhibitor resistance in different cancers.

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Bromodomain and HDAC inhibitors equivalently suppress PI3K/AKT inhibition resistance in cancers

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Bromodomain and HDAC inhibitors equivalently suppress PI3K/AKT inhibition resistance in cancers

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Tissue-Engineered Disease Modeling of Lymphangioleiomyomatosis Exposes a Therapeutic Vulnerability to HDAC Inhibition

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