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PXD026291

PXD026291 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleSynergistic PIM kinase and proteasome inhibition in MYC-overexpressing triple-negative breast cancer
DescriptionTriple-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.
HostingRepositoryMassIVE
AnnounceDate2021-09-14
AnnouncementXMLSubmission_2021-09-14_18:39:18.438.xml
DigitalObjectIdentifier
ReviewLevelNon peer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterCho Byoung-Kyu
SpeciesList scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentQ Exactive HF
Dataset History
RevisionDatetimeStatusChangeLog Entry
02021-05-26 07:43:51ID requested
12021-09-14 18:39:18announced
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 affiliationNorthwestern University
contact emailyoung.goo@northwestern.edu
lab head
Cho Byoung-Kyu
contact affiliationNorthwestern University
contact emailbyoungkyu.cho@northwestern.edu
dataset submitter
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