PXD050707

PXD050707 is an original dataset announced via ProteomeXchange.

Dataset Summary

Title	Gemcitabine and ATR inhibitors synergize to kill PDAC cells by blocking DNA damage response
Description	The DNA-damaging agent gemcitabine (GEM) is a first-line treatment for pancreatic cancer but chemoresistance is frequently observed. Several clinical trials investigate the efficacy of GEM in combination with targeted drugs including kinase inhibitors but the experimental evidence for such rational is often unclear. Here, we phenotypically screened 13 human pancreatic adenocarcinoma (PDAC) cell lines against GEM in combination with 140 clinical kinase inhibitors and observed strong synergy for the ATR inhibitor Elimusertib in most cell lines. Dose-dependent phosphoproteome profiling of four ATR inhibitors following DNA damage induction by GEM revealed a strong block of the DNA damage response pathway including phosphorylated pS468 of CHEK1 as the underlying mechanism of drug synergy. The current work provides a strong rationale for why the combination of GEM and ATR inhibition may be useful for the treatment of PDAC patients and constitutes a rich phenotypic and molecular resource for further investigating effective drug combinations.
HostingRepository	MassIVE
AnnounceDate	2024-12-13
AnnouncementXML	Submission_2024-12-13_12:34:02.151.xml
DigitalObjectIdentifier
ReviewLevel	Non peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Stefanie Hoefer
SpeciesList	scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606;
ModificationList	phosphorylated residue; iodoacetamide derivatized residue; monohydroxylated residue; acetylated residue
Instrument	Orbitrap Fusion Lumos

Dataset History

Revision	Datetime	Status	ChangeLog Entry
0	2024-03-18 01:33:37	ID requested
⏵ 1	2024-12-13 12:34:02	announced

Publication List

no publication

no publication

Keyword List

submitter keyword: decryptM, Phosphorylation, Kinase Inhibitor, Kinobeads, Pancreatic cancer

submitter keyword: decryptM, Phosphorylation, Kinase Inhibitor, Kinobeads, Pancreatic cancer

Contact List

Bernhard Kuster
contact affiliation	Technical University of Munich (TUM)
contact email	kuster@tum.de
lab head
Stefanie Hoefer
contact affiliation	TU Munich
contact email	stefanie.hoefer@tum.de
dataset submitter

Full Dataset Link List

MassIVE dataset URI
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MassIVE dataset 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://massive.ucsd.edu/v07/MSV000094340/