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Anticancer activity of RAS-GTP inhibition in cholangiocarcinoma

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE318391 | GEO | 2026/03/30

REPOSITORIES: GEO

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Anticancer activity of RAS-GTP inhibition in cholangiocarcinoma [Mouse_hKPR.KPCHR_Sep25]

Project description:About 25% of cholangiocarcinoma (CCA) patients harbor KRAS mutations, being potentially amenable to direct KRAS inhibitors. Here, we investigated the activity of RAS(ON) multi-selective inhibitors, which target the active, GTP-bound state of both mutant and wild-type variants of canonical RAS isoforms, in CCA preclinical models and patients. RAS(ON) multi-selective inhibitors yield strong anticancer responses in cell- and patient-derived xenografts and in immunocompetent allograft models. Consistently, we describe responses to the RAS(ON) multi-selective inhibitor daraxonrasib in two KRASG12X patients with advanced CCA. RAS-GTP inhibition also potentiates the activity of the current standard-of-care CCA therapy to prolong survival in cell-derived human xenografts and mouse allografts. Furthermore, we demonstrate that both intrinsic and acquired resistance to RAS(ON) multi-selective inhibitors mainly rely on reconstitution of RAS signalling. Overall, our findings indicate that KRAS mutant CCA is addicted to RAS signalling for proliferation and support the potential clinical evaluation of RAS-GTP inhibition in CCA.

2026-03-30 | GSE318390 | GEO

Anticancer activity of RAS-GTP inhibition in cholangiocarcinoma [Mouse_iAKP_Abr24]

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Anticancer activity of RAS-GTP inhibition in cholangiocarcinoma [Human_Abr24]

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Anticancer activity of RAS-GTP inhibition in cholangiocarcinoma

Project description:Anticancer activity of RAS-GTP inhibition in cholangiocarcinoma

| PRJNA1418659 | ENA

Anticancer activity of RAS-GTP inhibition in cholangiocarcinoma [Mouse_iAKP_Abr24]

Project description:Anticancer activity of RAS-GTP inhibition in cholangiocarcinoma [Mouse_iAKP_Abr24]

| PRJNA1418665 | ENA

Anticancer activity of RAS-GTP inhibition in cholangiocarcinoma [Mouse_hKPR.KPCHR_Sep25]

Project description:Anticancer activity of RAS-GTP inhibition in cholangiocarcinoma [Mouse_hKPR.KPCHR_Sep25]

| PRJNA1418668 | ENA

Anticancer activity of RAS-GTP inhibition in cholangiocarcinoma [Human_Abr24]

Project description:Anticancer activity of RAS-GTP inhibition in cholangiocarcinoma [Human_Abr24]

| PRJNA1418666 | ENA

Epigenetic Reprogramming of mutant RAS-driven Rhabdomyosarcoma via MEK Inhibition

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

2018-04-01 | GSE85171 | GEO

Effect of YAP overexpression on HuCCT1 cholangiocarcinoma cell line transcriptome

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2015-10-27 | E-GEOD-61767 | biostudies-arrayexpress

Pharmaceutical inhibition of RAS overcomes cytokine mediated resistance to FLT3 inhibition in FLT3-ITD+ AML

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

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