MassIVE MSV000087521

Complete Public PXD026291

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. [doi:10.25345/C52530] [dataset license: CC0 1.0 Universal (CC0 1.0)]

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

Contact

Principal Investigators:
(in alphabetical order)
Young Ah Goo, Northwestern University, United States
Submitting User: cbk562
Number of Files:
Total Size:
Spectra:
Subscribers:
 
Owner Reanalyses
Experimental Design
    Conditions:
    Biological Replicates:
    Technical Replicates:
 
Identification Results
    Proteins (Human, Remapped):
    Proteins (Reported):
    Peptides:
    Variant Peptides:
    PSMs:
 
Quantification Results
    Differential Proteins:
    Quantified Proteins:
 
Browse Dataset Files Browse Results
 
FTP Download Link (click to copy):

- Dataset Reanalyses


+ Dataset History


Click here to queue conversion of this dataset's submitted spectrum files to open formats (e.g. mzML). This process may take some time.

When complete, the converted files will be available in the "ccms_peak" subdirectory of the dataset's FTP space (accessible via the "FTP Download" link to the right).
Number of distinct conditions across all analyses (original submission and reanalyses) associated with this dataset.

Distinct condition labels are counted across all files submitted in the "Metadata" category having a "Condition" column in this dataset.

"N/A" means no results of this type were submitted.
Number of distinct biological replicates across all analyses (original submission and reanalyses) associated with this dataset.

Distinct replicate labels are counted across all files submitted in the "Metadata" category having a "BioReplicate" or "Replicate" column in this dataset.

"N/A" means no results of this type were submitted.
Number of distinct technical replicates across all analyses (original submission and reanalyses) associated with this dataset.

The technical replicate count is defined as the maximum number of times any one distinct combination of condition and biological replicate was analyzed across all files submitted in the "Metadata" category. In the case of fractionated experiments, only the first fraction is considered.

"N/A" means no results of this type were submitted.
Originally identified proteins that were automatically remapped by MassIVE to proteins in the SwissProt human reference database.

"N/A" means no results of this type were submitted.
Number of distinct protein accessions reported across all analyses (original submission and reanalyses) associated with this dataset.

"N/A" means no results of this type were submitted.
Number of distinct unmodified peptide sequences reported across all analyses (original submission and reanalyses) associated with this dataset.

"N/A" means no results of this type were submitted.
Number of distinct peptide sequences (including modified variants or peptidoforms) reported across all analyses (original submission and reanalyses) associated with this dataset.

"N/A" means no results of this type were submitted.
Total number of peptide-spectrum matches (i.e. spectrum identifications) reported across all analyses (original submission and reanalyses) associated with this dataset.

"N/A" means no results of this type were submitted.
Number of distinct proteins quantified across all analyses (original submission and reanalyses) associated with this dataset.

Distinct protein accessions are counted across all files submitted in the "Statistical Analysis of Quantified Analytes" category having a "Protein" column in this dataset.

"N/A" means no results of this type were submitted.
Number of distinct proteins found to be differentially abundant in at least one comparison across all analyses (original submission and reanalyses) associated with this dataset.

A protein is differentially abundant if its change in abundance across conditions is found to be statistically significant with an adjusted p-value <= 0.05 and lists no issues associated with statistical tests for differential abundance.

Distinct protein accessions are counted across all files submitted in the "Statistical Analysis of Quantified Analytes" category having a "Protein" column in this dataset.

"N/A" means no results of this type were submitted.