PXD047912

PXD047912 is an original dataset announced via ProteomeXchange.

Dataset Summary

Title	Cell specific models reveal conformation-specific RAF inhibitor combinations that synergistically inhibit ERK signaling in pancreatic cancer cells
Description	Pancreatic ductal adenocarcinoma (PDAC) presents significant challenges for targeted clinical interventions due to prevalent KRAS mutations, rendering PDAC resistant to RAF and MEK inhibitors (RAFi and MEKi). In addition, responses to targeted therapies vary between patients. Here, we explored the differential sensitivities of PDAC cell lines to RAFi and MEKi and developed an isogenic pair comprising the most sensitive and resistant PDAC cells. To simulate patient or tumor specific variations, we constructed cell line-specific mechanistic models based on protein expression profiling and differential properties of KRAS mutants. These models predicted synergy between two RAFi with different conformation specificity (type I½ and type II RAFi) in inhibiting ppERK and reducing PDAC cell viability. This synergy was experimentally validated across all four studied PDAC cell lines. Our findings underscore the need for combination approaches to inhibit the ERK pathway in PDAC.
HostingRepository	PRIDE
AnnounceDate	2024-10-24
AnnouncementXML	Submission_2024-10-24_08:37:34.504.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Kieran Wynne
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	timsTOF Pro

Dataset History

Revision	Datetime	Status	ChangeLog Entry
0	2023-12-18 15:25:57	ID requested
1	2024-09-03 13:59:13	announced
⏵ 2	2024-10-24 08:37:34	announced	2024-10-24: Updated project metadata.

Publication List

10.1016/J.CELREP.2024.114710;

10.1016/J.CELREP.2024.114710;

Keyword List

submitter keyword: Pancreatic ductal adenocarcinoma
RAF inhibitors
drug combination
MAPK pathway
synergy
targeted therapy resistance
KRAS mutation

submitter keyword: Pancreatic ductal adenocarcinoma

RAF inhibitors

drug combination

MAPK pathway

synergy

targeted therapy resistance

KRAS mutation

Contact List

Boris Kholodenko
contact affiliation	Full Professor of Systems Biology and Director of Computational Modelling Systems Biology Ireland, University College Dublin, Dublin, Ireland. Conway Institute of Biomolecular & Biomedical Research,University College Dublin, Dublin, Ireland. School of Medicine and Medical Science, University College Dublin, Dublin, Ireland. Department of Pharmacology, Yale University School of Medicine, New Haven, CT, USA
contact email	boris.kholodenko@ucd.ie
lab head
Kieran Wynne
contact affiliation	University College Dublin
contact email	kieran.wynne1@ucd.ie
dataset submitter

Full Dataset Link List

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/09/PXD047912
PRIDE project URI

Dataset FTP location
NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/09/PXD047912

PRIDE project URI

Repository Record List

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