Evolving stratification and biomarker discovery in cancer research with technological advancement of proteomics: 35 years and counting.

Proteome, the molecular product of regulatory diktat of the cellular machinery, predicts the behaviour and progression of cancers. Designing effective molecular therapies based on proteins with comprehensive patient stratification remains the mainstay of every translational research. Research on the proteome involves a) identification of biomarkers that, with utmost sensitivity and specificity, reveal significant insights into the disease state and b) understanding the mechanistic underpinnings and rewiring of cellular signaling pathways that drive a particular cancerous pathology. In this review, we give a comprehensive description of the evolution of mass spectrometer-based methods, including labeling strategies available to study the proteome and post-translational modifications in response to various perturbations. We summarize their utility in understanding complex processes of cancers, advance research on cancer therapy by decoding novel biomarkers, identify therapy resistance drivers, and enhance spatial attributes of tumor microenvironment by single-cell proteomics. Finally, some of the challenges in the currently used methods have been discussed.