Therapeutic value of glycosaminoglycans in cancer.
Glycosaminoglycans are unbranched polysaccharides composed of repeating units of alternating uronic acids and amino sugars. Most glycosaminoglycans are covalently attached to core proteins to form proteoglycans. Posttranslational modifications result in specific motifs that bind to a large variety of ligands, thus regulating growth factor signaling, cellular behavior, inflammation, angiogenesis, and the proteolytic environment. Dysregulated expression of glycosaminoglycans is present in cancer and reported to correlate with clinical prognosis in several malignant neoplasms. Recent knowledge on the biological roles of these molecules in cancer biology, tumor angiogenesis, and metastasis has promoted the development of drugs targeting them. Pharmaceutical approaches include the use of chemically modified heparins and glycosaminoglycans with defined structures, combination of inhibitors of glycosaminoglycan biosynthesis and polyamine depletion, and biologically active glycosaminoglycan-binding peptides. In addition, glycosaminoglycans are used as tumor-specific delivery and targeting vehicles for toxins and chemotherapeutics. Encouraging results in animal studies and clinical trials show the clinical relevance of glycosaminoglycan-based drugs and the use of glycosaminoglycans as therapeutic targets.
Yip
George W
GW
Department of Anatomy, National University of Singapore, Singapore.
Smollich
Martin
M
Götte
Martin
M
D000818:Animals; D006025:Glycosaminoglycans / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000627:therapeutic use*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism*
D006025:Glycosaminoglycans