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Radiation combined with KRAS-MEK inhibitors enhances anticancer immunity in KRAS-mutated tumor models [CT26 RNA-seq]

ABSTRACT: Radiation combined with KRAS-MEK inhibitors enhances anticancer immunity in KRAS-mutated tumor models [CT26 RNA-seq]

PROVIDER: PRJNA862374 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR20648816.fastq.gz	Fastqsanger.gz
	SRR20648817.fastq.gz	Fastqsanger.gz
	SRR20648818.fastq.gz	Fastqsanger.gz
	SRR20648819.fastq.gz	Fastqsanger.gz
	SRR20648820.fastq.gz	Fastqsanger.gz

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Radiation combined with KRAS-MEK inhibitors enhances anticancer immunity in KRAS-mutated tumor models [CT26 RNA-seq]

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Radiation combined with KRAS-MEK inhibitors enhances anticancer immunity in KRAS-mutated tumor models [LLC RNA-seq]

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Radiation combined with KRAS-MEK inhibitors enhances anticancer immunity in KRAS-mutated tumor models

Project description:Radiation combined with KRAS-MEK inhibitors enhances anticancer immunity in KRAS-mutated tumor models

| PRJNA862365 | ENA

Radiation combined with KRAS-MEK inhibitors enhances anticancer immunity in KRAS-mutated tumor models [LLC RNA-seq]

Project description:Radiation combined with KRAS-MEK inhibitors enhances anticancer immunity in KRAS-mutated tumor models [LLC RNA-seq]

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BI-3406, a potent and selective SOS1::KRAS interaction inhibitor, is effective in KRAS-driven cancers through combined MEK inhibition

Project description:KRAS is the most frequently mutated driver of pancreatic, colorectal, and non-small cell lung cancers. Direct KRAS blockade has proven challenging and inhibition of a key downstream effector pathway, the RAF-MEK-ERK cascade, has shown limited success due to activation of feedback networks that keep the pathway in check. We hypothesized that inhibiting SOS1, a KRAS activator and important feedback node, represents an effective approach to treat KRAS-driven cancers. We report the discovery of a highly potent, selective and orally bioavailable small-molecule SOS1 inhibitor, BI-3406, that binds to the catalytic domain of SOS1 thereby preventing the interaction with KRAS. BI-3406 reduces formation of GTP-loaded RAS and limits cellular proliferation of a broad range of KRAS-driven cancers. Importantly, BI-3406 attenuates feedback reactivation induced by MEK inhibitors and thereby enhances sensitivity of KRAS-dependent cancers to MEK inhibition. Combined SOS1 and MEK inhibition represents a novel and effective therapeutic concept to address KRAS-driven tumors.

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