Harnessing changes in cellular glycosylation in new cancer treatment strategies.
The majority of proteins are modified in post-translational events and one of the most common of these is glycosylation. Many reports describe alterations to the normal cellular glycosylation in cancer but detailed knowledge of the underlying structures and mechanisms that result in the altered glycosylation of cancer glycoproteins have been hindered by the inherent complexity of glycans themselves. Improved analytical tools for the study of glycosylation and application of molecular techniques for the characterisation of the genes encoding glycosyltransferases have, however, enabled the structural identification of some of the cancer-associated changes in glycosylation. The observed alterations in protein glycosylation in cancer have led to clinical trials in which glycans on cancer cell-surface proteins are targeted. These new approaches to cancer treatment include immunotherapy and carbohydrate-processing inhibitor-based strategies. Compounds that mimic glycans involved in the metastatic dissemination of cancer are also actively sought. The results that have been obtained and the long-term potential of these new approaches are discussed in this review article.
Department of Molecular and Applied Biosciences, School of Biosciences, University of Westminster, 115 New Cavendish St., London, W1W 6UW, UK. m.v.dwek@westminster.ac.uk
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Brooks
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D006023:Glycoproteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D006031:Glycosylation / Q000187:drug effects; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism*
D000970:Antineoplastic Agents; D006023:Glycoproteins