PXD005734
PXD005734 is an original dataset announced via ProteomeXchange.
Dataset Summary
Title | ABPP of Ibrutinib Resistance in B Cell Malignancies |
Description | Ibrutinib,a novel Bruton'styrosine kinase inhibitor, demonstrated high response rates in B-cell lymphomas but a growing number of ibrutinib treated patients relapse with resistance, fulminant progression and accelerated mortality. Using chemical proteomics and a high-throughput ex vivo assay in a reconstructed tumor microenvironment (TME), we determined the molecular basis for ibrutinib activity and mechanism of acquired ibrutinib resistance. Reciprocal activation of PI3K-AKT-mTOR and integrin β1 signaling were identified as a signaling hub of kinome for ibrutinib resistance, resulting in enforced TME-lymphoma interactions, promoting mantle cell lymphoma (MCL) growth and drug resistance. Combinatorial disruption of BCR signaling and ibrutinib resistance associated pathways led to release of MCL cells from TME, reversal of drugresistance and enhanced anti-MCL activity in murine and patient-derived xenograft models. This study integrated TME-mediated de-novo and acquired drug resistance mechanisms and provides the rationale for novel combination therapeutic strategy against MCL and other B cell malignancies. |
HostingRepository | PRIDE |
AnnounceDate | 2018-10-26 |
AnnouncementXML | Submission_2018-10-26_10:27:07.xml |
DigitalObjectIdentifier | https://dx.doi.org/10.6019/PXD005734 |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Supported dataset by repository |
PrimarySubmitter | John Koomen |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | Oxidation; Biotin:Thermo-88310; Carbamidomethyl |
Instrument | LTQ Orbitrap |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
---|---|---|---|
0 | 2017-01-17 05:35:29 | ID requested | |
⏵ 1 | 2018-10-26 10:27:08 | announced |
Publication List
Zhao X, Lwin T, Silva A, Shah B, Tao J, Fang B, Zhang L, Fu K, Bi C, Li J, Jiang H, Meads MB, Jacobson T, Silva M, Distler A, Darville L, Zhang L, Han Y, Rebatchouk D, Di Liberto M, Moscinski LC, Koomen JM, Dalton WS, Shain KH, Wang M, Sotomayor E, Tao J, Unification of de novo and acquired ibrutinib resistance in mantle cell lymphoma. Nat Commun, 8():14920(2017) [pubmed] |
Keyword List
curator keyword: Biomedical |
submitter keyword: activity-based protein profiling, LC-MS/MS, B-cell cancers, Ibrutinib |
Contact List
Jianguo Tao, MD/PhD | |
---|---|
contact affiliation | Moffitt Cancer Center Tampa, FL, USA |
contact email | jianguo.tao@moffitt.org |
lab head | |
John Koomen | |
contact affiliation | Moffitt Cancer Center |
contact email | john.koomen@moffitt.org |
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/2018/10/PXD005734 |
PRIDE project URI |
Repository Record List
[ + ]