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Kinase Inhibitor Pulldown Assay Identifies a Chemotherapy Response Signature in Triple-negative Breast Cancer Based
Junkai Wang1,2, Alexander B Saltzman3, Eric J Jaehnig1
1Lester and Sue Smith Breast Center and Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas.
Cancer Research Communications
|August 17, 2023
Summary
A novel assay identified a purine-binding protein (PBP) signature associated with pathologic complete response (pCR) in triple-negative breast cancer (TNBC). This signature predicts chemotherapy sensitivity and outcomes, offering potential for personalized treatment strategies.
Area of Science:
- Biochemistry
- Oncology
- Proteomics
Background:
- Triple-negative breast cancer (TNBC) lacks targeted therapies, with chemotherapy efficacy varying among patients.
- Identifying predictive biomarkers for pathologic complete response (pCR) is crucial for advancing precision treatment in TNBC.
Purpose of the Study:
- To deploy a mass spectrometry (MS)-based kinase inhibitor pulldown assay (KIPA) to identify therapeutic targets in TNBC.
- To discover novel biomarkers associated with pCR in response to neoadjuvant chemotherapy.
Main Methods:
- Utilized KIPA on tumor lysates from 43 TNBC patients undergoing neoadjuvant chemotherapy.
- Analyzed identified purine-binding proteins (PBPs) for association with pCR.
- Validated a seven-gene PBP signature in independent mRNA-based TNBC datasets.
Main Results:
- KIPA did not identify kinases associated with lack of pCR.
- A seven-member PBP signature was enriched in pCR-associated samples (P < 0.01).
- The PBP signature correlated with chemotherapy sensitivity and favorable outcomes in TNBC.
Conclusions:
- KIPA identified a unique PBP signature associated with cytotoxic drug response in TNBC.
- The PBP signature has potential for clinical trial stratification, guiding therapy escalation or de-escalation based on pCR probability.
