Dataset Information

Multi-omics characterization of MEK inhibitor resistant pancreatic cancer based on a genetically engineered mouse model-derived in vitro system

ABSTRACT: Tumor heterogeneity and therapy resistance are hallmarks of pancreatic ductal adenocarcinoma (PDAC). Emerging evidence supports treatment-induced resistance to be a multifactorial process mediated by cellular plasticity involving epigenetic regulation. Here, we used a multi-omics approach to analyze in detail molecular mechanisms underlying MEK inhibitor (MEKi) resistance. Therefore, we characterized different cell stages (parental, MEKi resistant, reverted after different passages of drug withdrawal) in primary cell lines derived from a genetic PDAC mouse model, thereby minimizing inter-individual heterogeneity that could distort genome-wide analyses.

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Primary Cell, Cell Culture, Pancreatic Ductal Carcinoma Cell

DISEASE(S): Pancreatic Ductal Adenocarcinoma

SUBMITTER: Kathrin Elisabeth Witzke

LAB HEAD: Barbara Sitek

PROVIDER: PXD018093 | Pride | 2024-01-26

REPOSITORIES: Pride

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Publications

Pancreatic cancer acquires resistance to MAPK pathway inhibition by clonal expansion and adaptive DNA hypermethylation.

Godfrey Laura K LK Forster Jan J Liffers Sven-Thorsten ST Schröder Christopher C Köster Johannes J Henschel Leonie L Ludwig Kerstin U KU Lähnemann David D Trajkovic-Arsic Marija M Behrens Diana D Scarpa Aldo A Lawlor Rita T RT Witzke Kathrin E KE Sitek Barbara B Johnsen Steven A SA Rahmann Sven S Horsthemke Bernhard B Zeschnigk Michael M Siveke Jens T JT

Clinical epigenetics 20240116 1

<h4>Background</h4>Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with poor prognosis. It is marked by extraordinary resistance to conventional therapies including chemotherapy and radiation, as well as to essentially all targeted therapies evaluated so far. More than 90% of PDAC cases harbor an activating KRAS mutation. As the most common KRAS variants in PDAC remain undruggable so far, it seemed promising to inhibit a downstream target in the MAPK pathway such as MEK1/2, but u ...[more]

PMID: 38229153

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Dataset Information

Multi-omics characterization of MEK inhibitor resistant pancreatic cancer based on a genetically engineered mouse model-derived in vitro system

Publications

Pancreatic cancer acquires resistance to MAPK pathway inhibition by clonal expansion and adaptive DNA hypermethylation.

Similar Datasets

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