Glycomics Meets Oncology: The Role of Mass Spectrometry in Cancer Research.

Glycosylation, the enzymatic addition of carbohydrate moieties to proteins and lipids, is a fundamental posttranslational modification that profoundly influences cellular processes. Altered glycosylation patterns represent a characteristic of malignant transformation, affecting tumor progression, immune evasion, metastasis, and response to therapy. The emerging field of glycomics aims to systematically characterize these glycan structures, providing insights into their biological roles and clinical relevance. Mass spectrometry (MS) has become an indispensable tool in cancer glycomics due to its sensitivity, specificity, and ability to resolve complex carbohydrate heterogeneity. In this context, this chapter explores how advanced MS techniques, including electrospray ionization (ESI) and chip-based ESI, matrix-assisted laser desorption/ionization (MALDI), ion mobility separation (IMS) MS, MS-imaging (MSI), liquid chromatography (LC)-MS, and tandem MS, enable comprehensive profiling of N- and O-glycans, glycolipids, glycoproteins and proteoglycans in cancer cells and patient samples. We discuss methodological approaches for glycan and glycoconjugate release, derivatization, and preparation for the MS analysis, as well as emerging strategies for N- and O-glycosylation mapping and detailed structural elucidation. Case studies illustrate how MS-based glycomics has identified cancer-specific glycan signatures with high potential as diagnostic, prognostic, and therapeutic biomarkers. By integrating glycomics with other omics technologies, scientists can uncover novel mechanisms of tumor biology and guide precision oncology. Overall, this book chapter illustrates that mass spectrometry is one of the most powerful platforms to translate the complex glycan landscape into actionable insights in cancer research.