Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Targeted KRAS G12V degradation elicits efficient and durable lung adenocarcinoma regression in vivo

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

ORGANISM(S): Mus musculus

PROVIDER: GSE301303 | GEO | 2026/05/14

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Targeted KRAS(G12V) degradation elicits efficient and durable lung adenocarcinoma regression in vivo

Project description:Recent drug discovery breakthroughs led to the approval of KRASG12C inhibitors in lung adenocarcinoma (LUAD). Unfortunately, clinical responses remain limited due to rapid resistance onset. Proteolysis-targeting chimeras (PROTACs) have emerged as promising alternatives to traditional inhibition. However, there is limited mechanistic understanding of KRAS degradation in vivo. Here, we developed a preclinical LUAD mouse model and demonstrated that targeted KRAS degradation induces rapid tumor regression. Transcriptional and histological analyses revealed a substantial remodeling of the tumor microenvironment. Notably, the low resistance rate observed during long-term treatment stems from proteolysis machinery dysregulation rather than KRAS absence adaptation, indicating resistance mechanisms distinct from KRAS inhibition. Our findings highlight the therapeutic potential of KRAS degradation in LUAD, offering insights into cell-intrinsic and extrinsic mechanisms driving durable antitumor responses and supporting further clinical exploration.

2026-05-13 | PXD058734 | Pride

Targeted KRAS G12V degradation elicits efficient and durable lung adenocarcinoma regression in vivo [R_invivo_invitro]

Project description:Recent drug discovery breakthroughs led to the approval of KRASG12C inhibitors in lung adenocarcinoma (LUAD). Unfortunately, clinical responses are often hampered by the rapid emergence of resistance. Proteolysis-targeting chimeras (PROTACs) have emerged as promising alternatives to traditional inhibition. However, there is limited mechanistic understanding of KRAS degradation in vivo. Here, we developed a preclinical LUAD mouse model and demonstrated that targeted oncogenic KRAS degradation induces rapid tumor regression primarily due to cancer cell-intrinsic mechanisms. Yet, transcriptional, histological, and immunophenotypic analyses revealed a substantial remodeling of the tumor microenvironment. Notably, disease relapse observed during prolongued degrader treatment stems from proteolysis machinery dysregulation, indicating resistance mechanisms distinct from those reported upon KRAS inhibition. Collectively, our findings highlight the therapeutic potential of KRAS degradation in LUAD, providing insights into both cell-intrinsic and -extrinsic mechanisms that accompany antitumor responses and support the continued clinical development of this approach.

2026-05-14 | GSE301620 | GEO

Targeted KRAS G12V degradation elicits efficient and durable lung adenocarcinoma regression in vivo [dTAG_expt3_RNAseq]

2026-05-14 | GSE326057 | GEO

Targeted KRAS G12V degradation elicits efficient and durable lung adenocarcinoma regression in vivo [dTAG_expt2_RNAseq]

2026-05-14 | GSE301302 | GEO

Targeted KRAS G12V degradation elicits efficient and durable lung adenocarcinoma regression in vivo [dTAG_expt1_RNAseq]

2026-05-14 | GSE301301 | GEO

Targeted degradation of oncogenic KRAS G12V triggers antitumor immunity in lung cancer

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

2024-12-18 | GSE234472 | GEO

Targeted degradation of oncogenic KRAS G12V triggers antitumor immunity in lung cancer.

Project description:We performed bulk-RNA sequencing analysis from KRAS G12V mouse tumor nodules from different treatment.