PXD026291

PXD026291 is an original dataset announced via ProteomeXchange.

Dataset Summary

Title	Synergistic PIM kinase and proteasome inhibition in MYC-overexpressing triple-negative breast cancer
Description	Triple-negative breast cancer (TNBC) is the breast cancer (BC) subtype with the poorest outcome. The PIM family of kinases has recently emerged as a factor that is both overexpressed in TNBC samples and associated with poor outcomes. Preclinical data suggest that TNBC that exhibits an elevated MYC oncoprotein expression (MYC+TNBC), accounting for 50% of TNBC cases, is sensitive to PIM inhibition. However, ongoing clinical observations indicate that the efficacy of PIM inhibitors as single agents may be limited in solid tumors, suggesting the need for combination therapies. We conducted drug combination screens to identify a combination that targets PIM and the 20S proteasome (the PIMi/20Si combination) as the most synergistic combination. Following the screening, we used a chemical genetic approach to reveal that the mechanisms of drug synergy involve disruption of protein homeostasis and obstruction of an adaptive resistance mechanism associated with proteasome inhibition. Thus, the PIMi/20Si combination could represent a rational combination therapy against MYC+ TNBC that is readily translatable to early-stage clinical investigations.
HostingRepository	MassIVE
AnnounceDate	2021-09-14
AnnouncementXML	Submission_2021-09-14_18:39:18.438.xml
DigitalObjectIdentifier
ReviewLevel	Non peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Cho Byoung-Kyu
SpeciesList	scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Dataset History

Revision	Datetime	Status	ChangeLog Entry
0	2021-05-26 07:43:51	ID requested
⏵ 1	2021-09-14 18:39:18	announced

Publication List

no publication

no publication

Keyword List

submitter keyword: Triple-negative breast cancer, Chemical genetics, PIM kinase inhibitor, proteasome inhibitors, protein homeostasis, MYC oncoprotein, rational combination therapy

submitter keyword: Triple-negative breast cancer, Chemical genetics, PIM kinase inhibitor, proteasome inhibitors, protein homeostasis, MYC oncoprotein, rational combination therapy

Contact List

Young Ah Goo
contact affiliation	Northwestern University
contact email	young.goo@northwestern.edu
lab head
Cho Byoung-Kyu
contact affiliation	Northwestern University
contact email	byoungkyu.cho@northwestern.edu
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/MSV000087521/