PXD023717

PXD023717 is an original dataset announced via ProteomeXchange.

Dataset Summary

Title	Combined Inhibition of AKT and KIT Restores Expression of Programmed Cell Death 4 (PDCD4) in Gastrointestinal Stromal Tumor
Description	AKT activation is a hallmark of IM resistance in GIST. The presence of an additional therapeutic agent could potentially suppress the growth and survival of a clone of cancer cells, which have developed resistance to IM. Simultaneous targeting of AKT in addition to inhibiting KIT with IM has potential to be a promising strategy to prevent the development of secondary resistance to IM. Our group has previously shown significantly enhanced combination effects of IM with MK-2206, an oral pan-AKT inhibitor, in an IM-sensitive xenograft model in vivo, as measured by extended disease stabilization and improved survival. In this study, we evaluated the efficacy of a new selective, allosteric pan-AKT inhibitor, ARQ 751 (Merck, ArQule) in both IM-sensitive and resistant GIST in vivo models, including a GIST patient-derived xenograft (PDX) possessing an exon 9 KIT mutation. We report superior activity of ARQ 751 in combination with IM in a panel of IM-sensitive and IM-resistant GIST cell lines in vitro. This activity is mediated by increased PDCD4 expression leading to increased apoptosis and cell cycle arrest. Furthermore, dual inhibition of KIT and AKT provided impressive diseases stabilization in IM-sensitive GIST xenografts and trends toward stabilization in IM-resistant models in vivo.
HostingRepository	MassIVE
AnnounceDate	2021-09-27
AnnouncementXML	Submission_2021-09-27_18:26:16.300.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Alexandre Rosa Campos
SpeciesList	scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606;
ModificationList	Oxidation; Acetyl
Instrument	Orbitrap Fusion Lumos

Dataset History

Revision	Datetime	Status	ChangeLog Entry
0	2021-01-20 23:27:58	ID requested
⏵ 1	2021-09-27 18:26:17	announced

Publication List

Kozinova M, Joshi S, Ye S, Belinsky MG, Sharipova D, Farma JM, Reddy SS, Litwin S, Devarajan K, Campos AR, Yu Y, Schwartz B, von Mehren M, Rink L, Combined Inhibition of AKT and KIT Restores Expression of Programmed Cell Death 4 (PDCD4) in Gastrointestinal Stromal Tumor. Cancers (Basel), 13(15):(2021) [pubmed]

Kozinova M, Joshi S, Ye S, Belinsky MG, Sharipova D, Farma JM, Reddy SS, Litwin S, Devarajan K, Campos AR, Yu Y, Schwartz B, von Mehren M, Rink L, Combined Inhibition of AKT and KIT Restores Expression of Programmed Cell Death 4 (PDCD4) in Gastrointestinal Stromal Tumor. Cancers (Basel), 13(15):(2021) [pubmed]

Keyword List

submitter keyword: Gastrointestinal stromal tumor , AKT, KIT, PDCD4

submitter keyword: Gastrointestinal stromal tumor , AKT, KIT, PDCD4

Contact List

Lori Rink
contact affiliation	Fox Chase Cancer Center
contact email	Lori.Rink@fccc.edu
lab head
Alexandre Rosa Campos
contact affiliation	SBP Medical Discovery Institute
contact email	arosacampos@sbpdiscovery.org
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/MSV000086739/