Mass spectrometry-based proteomics of single cells and organoids: The new generation of cancer research

Mass spectrometry (MS)-based proteomics is becoming a widely used technique for proteome characterization. Remarkable improvements in the resolution and sensitivity of MS instruments have enabled MS to address an ever-increasing array of biological questions. Nevertheless, the intrinsic cellular heterogeneity of biological systems continues to be a hurdle in MS-based proteomics for cancer research. MS-based proteomics of 3D cellular models and single-cell systems are being used as an effective analysis technique to characterize cellular heterogeneity among cancer cells. Proteomic analysis of 3D cellular models and single-cell systems provides a correlation between cellular heterogeneity and patient-specific responses to chemotherapy drugs, leading to effective and less toxic cancer treatments. Here, we review the pioneering achievements in MS-based proteomic analysis of 3D cell models and single-cell systems. Additionally, we provide insights into the contribution of MS-based proteomics, from examining tumoroid and single-cell systems to the development of precision medicine for cancer treatment. • MS-based proteomics helps understand cancer diagnosis, prognosis, and pathogenesis. • Advances in MS technology and its contributions to proteome research are discussed. • Challenges faced by MS-based proteomics capturing cancer complexity are described. • Proteomics based treatment from 3D organoids may be more effective and less toxic. • Technical development in single-cell proteomics from cancer cells are discussed.