Rebecca C. Poulos

Survival rates in some paediatric cancers have improved greatly over recent decades, in part due to the identification of diagnostic, prognostic and predictive molecular signatures, and the development of risk‐directed therapies. However, other paediatric cancers have proved difficult to treat, and there is an urgent need to identify novel biomarkers that reveal therapeutic opportunities. The proteome is the total set of expressed proteins present in a cell or tissue at a point in time, and is vastly more dynamic than the genome. Proteomics holds significant promise for cancer research, as proteins are ultimately responsible for cellular phenotype and are the target of most anticancer drugs. Here, we review the discoveries, opportunities and challenges of proteomic analyses in paediatric cancer, with a focus on mass spectrometry (MS)‐based approaches. Accelerating incorporation of proteomics into paediatric precision medicine has the potential to improve survival and quality of life for children with cancer.