Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5904_Библиотеки_им_академика_М_И_Перельмана

both the glycan and peptide portions can be obtained through distinct yet comple­mentary tandem fragmentation strategies. Indeed, hybrid fragmentation methods

Glycans undoubtedly play an essential role in maintaining mammalian cell homeo­stasis. Strategically localized at the interface of a cell and its surrounding microen­vironment, glycans act as crucial molecular gatekeepers, actively governing virtually every cellular process. Moreover, since the posttranslational glycosylation cellular process is highly sensitive to a cell’s physiological state, glycans have been widely established as robust molecular reporters of pathological conditions and, in particu­lar, of the neoplastic transformation of human tissues. The aberrant expression of cancer‐specific glycan antigens by neoplastic cells, which stems from a variety of dysregulated mechanisms affecting the cellular glycosylation machinery, has been linked to the majority of malignant features supporting tumor cell survival, prolif­eration, differentiation, immune evasion, and local or distant organ dissemination. At the cellular level, TACAs drive malignant transformation by either disrupting the

homeostatic functions of tumor‐suppressive elements or by enhancing the onco-

genic properties of proteins controlling cell adhesion, programmed cell death, mito­genic signaling, and extracellular communication. However, the mechanistic basis underlying such alterations, as well as the functional impact that these may have on tumor onset, development, and metastatic spread, warrant further investigation. Indeed, several biosynthetic and structural features of glycans pose unique chal­lenges to their compositional characterization, structural elucidation, carrier assign­ment, and functional study. The vast array of monosaccharide substrate donors and transporters and the partial redundant and overlapping specificities depicted by GTs and glycosidases exponentially increase the structural complexity of the human gly­cosylation landscape. Moreover, the nontemplate‐driven nature of glycosylation greatly hinders the unequivocal analytical‐based structural elucidation of complex glycan chains. In recent years, we have witnessed the exponential technological development of cellular‐, imaging‐, and analytical‐based tools and platforms that have been instrumental in the unprecedented association between a glycan struc­ture and its function within complex biological systems. The rapidly expanding tool­box of gene editing technologies has allowed the generation of cellular and animal models depicting cleaner and well‐defined glycosylation backgrounds in which the study of glycan biosynthesis and function can be performed in the absence of con­founding factors such as GT redundant and compensatory activity. Increasingly complex imaging systems have prompted the comprehensive characterization of glycan expression patterns and distribution across histologically defined regions, as well as the identification and mapping of tumor‐relevant glycan–protein interac­tions at the single complex level, in tissue specimens from oncological patients. The emerging glycan microarray technology has fueled the high‐throughput interroga­tion and dissection of the glycan‐binding specificities of disease‐relevant carbohy­drate‐based molecular interactions actively underpinning numerous features of malignant cells, including evasion to immune recognition and surveillance. The MS‐based elucidation of the composition, 3D structure, and site of attachment of cancer‐associated glycan antigens has the potential to revolutionize the structure‐ guided design and optimization of cancer therapeutics. In conclusion, glycans undeniably represent a novel set of tools that will become indispensable in the field of modern‐era precision oncology, either as robust molecular biomarkers bearing diagnostic, prognostic, predictive, and stratifying value, or as promising targets for the delivery of personalized anticancer therapeutic agents.