Addressing Cellular Heterogeneity in Cancer through Precision Proteomics

Cells exhibit a broad spectrum of functions driven by differences in molecular phenotype. Understanding the heterogeneity between and within cell types has led to advances in our ability to diagnose and manipulate biological systems. Heterogeneity within and between tumors still poses a challenge to the development and efficacy of therapeutics. In this Perspective we review the toolkit of protein-level experimental approaches for investigating cellular heterogeneity. We describe how innovative approaches and technical developments have supported the advent of bottom-up single-cell proteomic analysis and present opportunities and challenges within cancer research. Finally, we introduce the concept of precision proteomics and discuss how the advantages and limitations of various experimental approaches render them suitable for different biological systems and questions.