Proteomics-driven precision oncology: from molecular profiling to biomarker discovery

Proteomics enables systematic, context-dependent characterization of the proteome, and has emerged as a cornerstone of precision cancer medicine. Although the systematical analysis of molecular profiling has transformed oncology over the past two decades, substantial heterogeneity in therapeutic responses still persists among patients with similar genetic alterations, highlighting the limitations of static genomic information. By directly interrogating signaling pathways and regulatory networks of proteins and post-translational modifications (PTMs) that drive tumor initiation, progression, and therapy resistance, proteomics bridges the gap between genomic alterations and phenotypic outcomes. Recent advances in mass spectrometry have enabled low-cost, high-throughput, and high-resolution proteomics from bulk to single cells, providing unprecedented insights into tumor heterogeneity. Integrative analysis of multi-omics, including genomics, transcriptomics and proteomics data, facilitates the construction of multidimensional molecular landscapes that reveal novel biomarkers and therapeutic targets. In this review, we summarize recent advances in proteomics-based biomarker discovery, highlight emerging single-cell and spatial proteomics technologies, and discuss future directions for integrating multi-omics, clinical information, and artificial intelligence to accelerate clinical translation.