Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

TARGETING KRAS SIGNALING AT THREE INDEPENDENT NODES LEADS TO COMPLETE AND DURABLE PANCREATIC CANCER REGRESSION [Methylation array]

ABSTRACT: TARGETING KRAS SIGNALING AT THREE INDEPENDENT NODES LEADS TO COMPLETE AND DURABLE PANCREATIC CANCER REGRESSION [Methylation array]

PROVIDER: PRJNA1134247 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Similar Datasets

TARGETING KRAS SIGNALING AT THREE INDEPENDENT NODES LEADS TO COMPLETE AND DURABLE PANCREATIC CANCER REGRESSION [Methylation array]

Project description:Pancreatic ductal adenocarcinoma (PDAC) has one of the lowest cancer survival rates. Although KRAS oncogenes are responsible for the initiation of most PDACs, thus far KRAS inhibitors have not changed their clinical outcome. Here, we describe a therapeutic strategy that combines inhibition of three independent signaling nodes involved in downstream (RAF1), upstream (EGFR) and orthogonal (STAT3) KRAS signaling pathways. Genetic elimination and/or pharmacological inhibition/degradation of these independent nodes in orthotopic mouse tumor models results in their complete and durable regression. The efficacy of this therapeutic strategy has also been validated in several patient-derived organoid (PDO) and xenograft (PDX) PDAC tumor models using a combination of a Pan-ERBB inhibitor (Afatinib), a selective STAT3 PROTAC (SD36) and a RAF1 shRNA. Importantly, this triple strategy did not induce significant toxicities. These results open the door to the development of novel targeted therapies for PDAC patients.

2024-10-15 | GSE271987 | GEO

TARGETING KRAS SIGNALING AT THREE INDEPENDENT NODES LEADS TO COMPLETE AND DURABLE PANCREATIC CANCER REGRESSION [RNA-seq]

2024-10-15 | GSE271518 | GEO

TARGETING KRAS SIGNALING AT THREE INDEPENDENT NODES LEADS TO COMPLETE AND DURABLE PANCREATIC CANCER REGRESSION [RNA-seq]

Project description:TARGETING KRAS SIGNALING AT THREE INDEPENDENT NODES LEADS TO COMPLETE AND DURABLE PANCREATIC CANCER REGRESSION [RNA-seq]

| PRJNA1132151 | ENA

Rapid Target Engagement of KRAS G12C Tricomplex Inhibitor RO3903 Overcomes Resistance and Drives Durable Tumor Regression

Project description:Cysteine chemoproteomics data for paper "Rapid Target Engagement of KRAS G12C Tricomplex Inhibitor RO3903 Overcomes Resistance and Drives Durable Tumor Regression"

2025-12-04 | MSV000100113 | MassIVE

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

Synergy of chemotherapy and macrophage depletion leads to T cell memory activation and durable triple negative breast cancer regression

Project description:Chemotherapy and macrophage depletion leads to T cell memory activation and durable triple negative breast cancer regression in p53 null mouse models.

2022-06-10 | GSE173260 | GEO

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

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 | GSE301302 | GEO

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

2026-05-14 | GSE301301 | GEO

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

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