Introduction: Given the poor prognosis of patients with TNBC, it is urgent to identify new biomarkers and therapeutic targets to enable personalized treatment strategies and improve patient survival. Comprehensive insights beyond genomic and transcriptomic analysis are crucial to improved outcomes for patients. As proteins are the workhorses of cellular function with their activity primarily regulated by phosphorylation, advanced phosphoproteomics techniques, such as mass spectrometry and antibody arrays, are essential for elucidating kinase signaling pathways that drive TNBC progression and contribute to therapy resistance.
Area covered: This review discusses the critical need to integrate phosphoproteomics into TNBC research, evaluates commonly used technologies and their applications, and explores their advantages and limitations. We highlight significant findings from phosphoproteomic analyses in TNBC and address the challenges of implementing these technologies into clinical practice.
Expert opinion: Rapid advances in phosphoproteomics analysis facilitate subtype stratification, adaptive response monitoring, and identification of biomarkers and therapeutic targets in TNBC. However, challenges in analyzing protein phosphorylation, especially in deep spatially resolved analysis of malignant cells and the tumor ecosystem, hinder the translation of phosphoproteomics to the CLIA setting. Nonetheless, phosphoproteomics offers a powerful tool that, when integrated into routine clinical practice, has the potential to revolutionize patient care.
Keywords: Phosphoproteomics; Reverse Phase Protein Array (RPPA); kinases; mass spectrometry; targeted therapy; triple-negative breast cancer (TNBC).