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Emerging roles of carbohydrates and glycomimetics in anticancer drug design
1Laboratory of Medicinal Chemistry, Division of Basic Sciences, National Cancer Institute, 37 Convent Dr. MSC4255, Bethesda, MD 20892-4255, USA. barchi@helix.nih.gov
Abstract:
Tumorigenesis is accompanied by marked changes in the expression and presentation of various macromolecules at the cell surface. These tumor-associated adjustments result from the differential expression of genes coding for the production or post-translational modifications of these macromolecules during transformation to a particular tumor phenotype. In turn, tumor cells acquire distinct biophysical properties which set them apart from their normal counterparts. Alterations of carbohydrate structures and their organization on the surface of neoplastic cells is a hallmark of the tumorigenic and, most notably, the metastatic phenotype. Carbohydrate-protein and carbohydrate-carbohydrate interactions are critical events in the progression, dissemination and invasion of cancer cells. Many cell-cell contacts and subsequent remodeling of the tumor microenvironment are mediated by cell-surface glycans. The discovery of agents that modulate these interactions or interfere with the processing of tumor associated oligosaccharides is a fervent area of research today. This review will highlight the current status of the use of carbohydrate-based compounds that are being evaluated as potential anticancer therapeutics. In addition, the use of structures based on glycopeptides and carbohydrate mimetics will also be discussed.
Insights
Tumorigenesis alters cell surface carbohydrates, impacting cancer progression and metastasis. Research explores carbohydrate-based compounds and mimetics as potential anticancer therapeutics targeting these changes.
Area of Science:
- Oncology
- Glycobiology
- Biochemistry
Background:
- Tumorigenesis involves significant changes in cell surface macromolecules.
- Altered gene expression during transformation leads to distinct tumor cell biophysical properties.
- Cell-surface glycans play a crucial role in cancer cell interactions and microenvironment remodeling.
Purpose of the Study:
- To review the current status of carbohydrate-based compounds as potential anticancer therapeutics.
- To discuss the evaluation of glycopeptides and carbohydrate mimetics in cancer treatment.
- To highlight the role of cell-surface carbohydrate alterations in tumorigenesis and metastasis.
Main Methods:
- Review of current research on carbohydrate-based anticancer agents.
- Analysis of studies evaluating glycopeptides and carbohydrate mimetics.
- Examination of the role of cell-surface glycans in cancer progression and invasion.
Main Results:
- Cell-surface carbohydrate alterations are a hallmark of tumorigenic and metastatic phenotypes.
- Carbohydrate-protein and carbohydrate-carbohydrate interactions are critical in cancer cell dissemination.
- The discovery of agents modulating these interactions is a key research area.
Conclusions:
- Carbohydrate-based compounds and mimetics show promise as anticancer therapeutics.
- Targeting cell-surface glycan modifications offers a potential strategy for cancer treatment.
- Further research is needed to fully evaluate these agents in cancer therapy.