Aberrant glycosylation patterns on cancer cells: Therapeutic opportunities for glycodendrimers/metallodendrimers oncology

Abstract

Despite exciting discoveries and progresses in drug design against cancer, its cure is still rather elusive and remains one of the humanities major challenges in health care. The safety profiles of common small molecule anti‐cancer therapeutics are less than at acceptable levels and limiting deleterious side‐effects have to be urgently addressed. This is mainly caused by their incapacity to differentiate healthy cells from cancer cells; hence, the use of high dosage becomes necessary. One possible solution to improve the therapeutic windows of anti‐cancer agents undoubtedly resides in modern nanotechnology. This review presents a discussion concerning multivalent carbohydrate–protein interactions as this topic pertains to the fundamental aspects that lead glycoscientists to tackle glyconanoparticles. The second section describes the detailed properties of cancer cells and how their aberrant glycan surfaces differ from those of healthy cells. The third section briefly describes the immune systems, both innate and adaptative, because the numerous displays of cell surface protein receptors necessitate to be addressed from the multivalent angles, a strength full characteristic of nanoparticles. The next chapter presents recent advances in glyconanotechnologies, including glycodendrimers in particular, as they apply to glycobiology and carbohydrate‐based cancer vaccines. This was followed by an overview of metallodendrimers and how this rapidly evolving field may contribute to our arsenal of therapeutic tools to fight cancer. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease

Design, Synthetic Strategies, and Therapeutic Applications of Heterofunctional Glycodendrimers

“…Therefore, and not surprisingly, the field of glycodendrimers, with their intrinsic multivalency and high affinity (avidity), has been exploited in the creation of powerful tools to provide therapeutic applications against cancer [44] that also include theranostics [45]. Several strategies can be applied to address this issue, amongst which, immune cell targeting through their well-studied mannoside receptors such as DC-SIGN [10], anti-carbohydrate antibodies and vaccines [40][41][42][43][44], screening microarrays using dendrimer's increased sensitivity [46,47], and notably anti-cancer vaccines. Interestingly, to this arsenal of glycodendrimers of therapeutic values against cancer, there is an additional avenue that was recently investigated.…”

“…Tumor-associated carbohydrate antigens (TACAs), originating from either glycolipids (gangliosides) [ 40 ] or O -linked mucin glycoproteins (MUCs) [ 41 , 42 , 43 , 44 ], have been extensively used as targeting agents for cancer immunotherapy. Therefore, and not surprisingly, the field of glycodendrimers, with their intrinsic multivalency and high affinity (avidity), has been exploited in the creation of powerful tools to provide therapeutic applications against cancer [ 44 ] that also include theranostics [ 45 ].…”

“…As stated above, owing to their over expression in a number of cancer cells, TACAs from the group of O -linked mucins have been the subject of intense activity to generate anti-carbohydrate cancer vaccines [ 41 , 42 , 43 , 44 ]. The group of Bay et al reported a fully synthetic anti-cancer vaccine for human use [ 50 , 51 ].…”

Drug design targeting active posttranslational modification protein isoforms

“…Drugs targeting protein ubiquitylation systems such as bortezomib and Carfilzomib of proteasome inhibitors and thalidomide and its analogs of cereblon protein binders have been approved for multiple myeloma and other types of cancer treatment 120,121 . Additionally, protein glycosylation is another important biological modification which is essential for many cellular functions such as signaling transduction, protein stability, transcription regulation, and cell survival 122–124 . Glycans associated with the cell surface receptors could substantially influence the structure and function of proteins through conformational change, protein turnover modulation, and intermolecular interactions.…”

FUT7 Promotes the Epithelial–Mesenchymal Transition and Immune Infiltration in Bladder Urothelial Carcinoma

“…Protein glycosylation, a critical and the most common post-translational modification form of proteins that involves in various physiological and pathological processes, 12,13 is an enzymatic reaction catalyzed by specific glycosyltransferases. 14,15 Abnormal glycosylation has been found to be closely associated with tumor proliferation, metastasis, and angiogenesis.…”