Emergent chemical and glycoengineering approaches for accessing the cancer glycoproteome

Every human cell is covered with a dense and complex array of sugar chains that impact a plethora of biological functions. In cancer, the cell surface witnesses a remodelling of these glycosidic protrusions involved in several cancer hallmarks. Moreover, this is often accompanied by the expression of altered proteoforms, resulting in distinct functions that contribute to tumour development and progression, and unique molecular signatures that may be explored for precision oncology and targeted therapeutics. In this chapter, we cover newly developed tools for the study of the cancer glycoproteome and glycan functionality. Namely, we address genetic engineering of glycogenes, novel glycoprotein-specific proteases, and bioorthogonal chemistry. State-of-the-art proteomic strategies are also described. Our goal is to provide an overview of the groundbreaking approaches that have accelerated our comprehension of glycosylation dynamics in cancer, outlining outstanding advancements towards clinical translation.