PXD043214

PXD043214 is an original dataset announced via ProteomeXchange.

Title	RAPID RESISTANCE TO BET INHIBITORS IS MEDIATED BY FGFR1 IN GLIOBLASTOMA
Description	Bromodomain and extra-terminal domain (BET) proteins are therapeutic targets in several cancers including the most common malignant adult brain tumor glioblastoma (GBM). Multiple small molecule inhibitors of BET proteins have been utilized in preclinical and clinical studies. Unfortunately, BET inhibitors have not shown efficacy in clinical trials enrolling GBM patients. One possible reason for this may stem from resistance mechanisms that arise after prolonged treatment within a clinical setting. However, the mechanisms and timeframe of resistance to BET inhibitors in GBM is not known. To identify the temporal order of resistance mechanisms in GBM we performed quantitative proteomics using multiplex-inhibitor bead mass spectrometry and demonstrated that resistance to BET inhibitors in GBM treatment occurs rapidly within hours and involves the fibroblast growth factor receptor 1 (FGFR1) protein. Small molecule inhibition of BET proteins and FGFR1 simultaneously induces synergy in reducing GBM tumor growth in vitro and in vivo. Further, FGFR1 knockdown synergizes with BET inhibitor mediated reduction of GBM cell proliferation. Collectively, our studies suggest that co-targeting BET and FGFR1 may dampen resistance mechanisms to yield a clinical response in GBM.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:45:46.390.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Nagi Ayad
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	6x(13)C labeled residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2023-06-22 09:43:45	ID requested
1	2024-06-16 01:38:10	announced
⏵ 2	2024-10-22 06:45:47	announced	2024-10-22: Updated project metadata.

10.1038/s41598-024-60031-8;

Jermakowicz AM, Kurimchak AM, Johnson KJ, Bourgain-Guglielmetti F, Kaeppeli S, Affer M, Pradhyumnan H, Suter RK, Walters W, Cepero M, Duncan JS, Ayad NG, RAPID resistance to BET inhibitors is mediated by FGFR1 in glioblastoma. Sci Rep, 14(1):9284(2024) [pubmed]

submitter keyword: FGFR1,Glioblastoma,BET Inhibitor

Nagi Ayad
contact affiliation	Georgetown University, USA
contact email	na853@georgetown.edu
lab head
Nagi Ayad
contact affiliation	Georgetown University
contact email	na853@georgetown.edu
dataset submitter

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/2024/06/PXD043214

PRIDE project URI

• PRIDE
  1. PXD043214
     1. Label: PRIDE project
     2. Name: RAPID RESISTANCE TO BET INHIBITORS IS MEDIATED BY FGFR1 IN GLIOBLASTOMA