Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

PANCREATIC DUCTAL ADENOCARCINOMAS RESISTANT TO KRAS INHIBITION ARE DRUGGABLE WITH AN ANTI-MUC1-C ADC

ABSTRACT: PANCREATIC DUCTAL ADENOCARCINOMAS RESISTANT TO KRAS INHIBITION ARE DRUGGABLE WITH AN ANTI-MUC1-C ADC

PROVIDER: PRJNA1246165 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Similar Datasets

PANCREATIC DUCTAL ADENOCARCINOMAS RESISTANT TO KRAS INHIBITION ARE DRUGGABLE WITH AN ANTI-MUC1-C ADC

Project description:Treatment of pancreatic ductal carcinomas (PDACs) has been advanced by the development of KRAS mutant inhibitors. Despite this progress, PDACs invariably develop resistance to these agents by mechanisms that largely remain unclear. The MUC1 gene, which encodes an oncogenic MUC1-C protein, is upregulated in PDAC KRAS G12D tumors. We report that treatment of PDAC cells with the selective KRAS G12D MRTX1133 inhibitor is associated with induction of MUC1-C expression. We show that KRAS G12D inhibition activates a MUC1-C/NF-B p65 auto-inductive pathway. Our results further demonstrate that MUC1-C drives resistance to MRTX1133 by activating the inflammatory IFN type I and II pathways. Of clinical relevance, targeting MUC1-C genetically and pharmacologically reverses MRTX1133 resistance and is synergistic in combination with MRTX1133 treatment. In leveraging MRTX1133-induced upregulation of MUC1-C expression, an anti-MUC1-C (M1C) antibody-drug conjugate (ADC) is highly effective against MRTX1133-resistant PDAC KRAS G12D cell lines, patient-derived organoids and PDX tumor xenograft models. These findings demonstrate that MUC1-C confers resistance of PDAC KRAS G12D mutant cells to MRTX1133 and identify MUC1-C as a target for M1C ADC treatment of PDAC patients who are refractory to MRTX1133 treatment.

2025-04-08 | GSE293756 | GEO

MUC1-C DICTATES NEUROENDOCRINE LINEAGE SPECIFICATION IN PANCREATIC DUCTAL ADENOCARCINOMAS

Project description:MUC1-C drives neuroendocrine lineage plasticity in pancreatic adenocarcinomas

2021-08-13 | GSE181961 | GEO

MUC1-C DICTATES NEUROENDOCRINE LINEAGE SPECIFICATION IN PANCREATIC DUCTAL ADENOCARCINOMAS

Project description:MUC1-C DICTATES NEUROENDOCRINE LINEAGE SPECIFICATION IN PANCREATIC DUCTAL ADENOCARCINOMAS

| PRJNA754087 | ENA

Treatment-Resistant Prostate Cancer Stem Cell Plasticity Governed by MUC1-C Uncovers a Common target for ADC Treatment

Project description:Androgen receptor positive prostate cancer (PC), castration resistant prostate cancer (CRPC) and neuroendocrine prostate cancer (NEPC) represent a spectrum of malignancies that invariably become resistant to treatment with targeted and cytotoxic agents. There is no known common pathway responsible for these pleotropic mechanisms of resistance. The MUC1 gene is aberrantly expressed in CRPC and NEPC in association with poor clinical outcomes. The present results demonstrate that the oncogenic MUC1-C protein is necessary for resistance of (i) PC cells to enzalutamide (ENZ), and (ii) CRPC and NEPC cells to docetaxel (DTX). We show that MUC1-C-mediated ENZ and DTX resistance is conferred by upregulation of aerobic glycolysis and suppression of reactive oxygen species (ROS) necessary for self-renewal capacity. Common dependence of these drug-resistant phenotypes on MUC1-C for the cancer stem cell (CSC) state thus identified a potential new target for their treatment. cIn this context, we further demonstrate that targeting MUC1-C with an antibody-drug conjugate (ADC) is highly effective in suppressing (i) self-renewal of drug-resistant CRPC and NEPC CSCs and (ii) growth of t-NEPC tumor xenografts derived from drug-resistant cells and a patient with refractory disease. These findings reveal a shared MUC1-C-dependent pathway in drug-resistant CRPC and NEPC progression and identify MUC1-C as a target for their treatment with an ADC.

2025-02-16 | GSE289308 | GEO

MUC1-C DEPENDENCE FOR PROGRESSION OF PANCREATIC NEUROENDOCRINE TUMORS IDENTIFIES A DRUGGABLE TARGET FOR TREATMENT OF THIS RARE CANCER

Project description:Patients with rare pancreatic neuroendocrine tumors (pNETs) have limited access to effective targeted agents and invariably succumb to progressive disease. MUC1-C is a druggable oncogenic protein linked to driving pan-cancers. There is no known involvement of MUC1-C in pNET progression. The present work was performed to determine if MUC1-C represents a potential target for advancing pNET treatment. We demonstrate that the MUC1 gene is upregulated in primary pNETs that progress with metastatic disease. In pNET cells, MUC1-C drives E2F- and MYC-signaling pathways necessary for survival. Targeting MUC1-C genetically and pharmacologically also inhibits self-renewal capacity and tumorigenicity. Studies of primary pNET tissues further demonstrate that MUC1-C expression associates with (i) advanced NET grade and pathological stage, (ii) metastatic disease, and (iii) decreased disease-free survival. These findings demonstrate that MUC1-C is necessary for pNET progression and is a novel target for treating these rare cancers with anti-MUC1-C agents under clinical development.

2024-05-21 | GSE267722 | GEO

Barrett's esophagus, Barrett's-associated adenocarcinomas and normal esophageal epithelium

Project description:Samples were obtained from 8 patients with Barrett's associated adenocarcinomas after transhiatal esophagectomy. Samples representative of the normal esophageal epithelium (N), Barrett’s esophagus (B) and esophageal adenocarcinomas (ADC) were obtained from every patient by experienced GI pathologists. RNA were extracted and samples were profiled for detection of genes differentially expressed in B and ADC relative to N and in ADC relative to B. Keywords: other

2004-11-18 | GSE1420 | GEO

Transcription profiling of esophagus samples from eight human patients with Barretts associated adenocarcinomas

Project description:Samples were obtained from 8 patients with Barrett's associated adenocarcinomas after transhiatal esophagectomy. Samples representative of the normal esophageal epithelium (N), BarrettÃ¢ÂÂs esophagus (B) and esophageal adenocarcinomas (ADC) were obtained from every patient by experienced GI pathologists. RNA were extracted and samples were profiled for detection of genes differentially expressed in B and ADC relative to N and in ADC relative to B.

2007-08-06 | E-GEOD-1420 | biostudies-arrayexpress

ADDICTION OF MERKEL CELL CARCINOMA TO MUC1-C IDENTIFIES A POTENTIAL NEW TARGET FOR TREATMENT OF THIS RECALCITRANT MALIGNANCY

Project description:MCCP and MCCN cells are addicted to the oncogenic MUC1-C protein. MUC1-C is a druggable target that may provide new opportunities for advancing MCC treatment.

2021-07-29 | GSE180876 | GEO

MUC1-C IS ESSENTIAL FOR INFLAMMATORY MEMORY OF TYROSINE KINASE INHIBITOR RESISTANCE IN NSCLC CELLS

Project description:This study identifies the oncogenic protein MUC1-C as a key driver of resistance to the EGFR tyrosine kinase inhibitor osimertinib in non-small cell lung cancers (NSCLCs).MUC1-C promotes resistance by activating STAT1 and type I/II interferon pathways, creating an inflammatory memory of the resistant phenotype. This memory is maintained via MUC1-C/STAT1 interaction at one enhancer region (pELS-1) and MUC1-C/JUN/PBAF at another (pELS-2) in the MUC1 gene. MUC1-C also mediates resistance to combination EGFR/MET inhibitors and a fourth-generation EGFR TKI (TQB3804). Importantly, targeting MUC1-C with an antibody-drug conjugate (M1C ADC) is effective both in vitro and in a patient-derived xenograft model, making MUC1-C a promising therapeutic target for TKI-refractory NSCLC.

2025-04-22 | GSE294981 | GEO

ADDICTION OF MERKEL CELL CARCINOMA TO MUC1-C IDENTIFIES A POTENTIAL NEW TARGET FOR TREATMENT OF THIS RECALCITRANT MALIGNANCY [MCC26]

Project description:MCCP and MCCN cells are addicted to the oncogenic MUC1-C protein. MUC1-C is a druggable target that may provide new opportunities for advancing MCC treatment.

2021-07-30 | GSE180891 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data