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 |
Keyword List
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 |
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/ |