Abstract

Simple SummaryAlterations in glycosylation are frequently observed in cancer cells. Different strategies have been proposed to increase drug delivery to the tumor site in order to improve the therapeutic efficacy of anti-cancer drugs and avoid collateral cytotoxicity. The exploitation of drug delivery approaches directed to cancer-associated glycans has the potential to pave the way for better and more efficient personalized treatment practices. Such strategies taking advantage of aberrant cell surface glycosylation patterns enhance the targeting efficiency and optimize the delivery of clinically used drugs to cancer cells, with major potential for the clinical applications.Innovative strategies have been proposed to increase drug delivery to the tumor site and avoid cytotoxicity, improving the therapeutic efficacy of well-established anti-cancer drugs. Alterations in normal glycosylation processes are frequently observed in cancer cells and the resulting cell surface aberrant glycans can be used as direct molecular targets for drug delivery. In the present review, we address the development of strategies, such as monoclonal antibodies, antibody–drug conjugates and nanoparticles that specific and selectively target cancer-associated glycans in tumor cells. The use of nanoparticles for drug delivery encompasses novel applications in cancer therapy, including vaccines encapsulated in synthetic nanoparticles and specific nanoparticles that target glycoproteins or glycan-binding proteins. Here, we highlight their potential to enhance targeting approaches and to optimize the delivery of clinically approved drugs to the tumor microenvironment, paving the way for improved personalized treatment approaches with major potential importance for the pharmaceutical and clinical sectors.

Highlights

  • Cancer remains one of the deadliest diseases and a major burden worldwide

  • Altered glycosylation encompasses the synthesis of prematurely truncated O-glycans, such as the single monosaccharide N-acetylgalactosamine (GalNAc; Tn antigen), sialyl Tn (STn) and the Thomsen–Friedenreich (T) antigen, as well as an increase in N-glycan β1,6-branching, terminal sialylation, including the biosynthesis of polysialic acid-containing structures, and both core and antennae-linked fucosylation

  • These tumor-associated glycan structures can be present on the surface of cancer cells, but they can be secreted or shed into the circulation and, serve as potential biomarkers of disease [13]

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Summary

Introduction

Cancer remains one of the deadliest diseases and a major burden worldwide. Over the last decades, early detection and effective treatment of cancer have been the main focus in the field. Targeting cancer cells is crucial to improve the efficiency of specific drugs, avoiding drug-induced toxicity in non-neoplastic tissues, and to aid in the detection of cancer cells and, improving diagnostics. For this reason, the development of novel and more efficient strategies to target malignant cells remains of major interest [4,5]. The current concept at the basis of precision oncology is that tumor-specific molecular abnormalities can be targeted with accurate, effective, and potentially less-toxic therapies. The use of aberrant glycans overexpressed by cancer cells have emerged as potential molecular candidates for the improvement of cancer targeted therapies [6,7]

Glycosylation in Cancer
Glycans with Specific Expression in Cancer
Truncated O-Glycans
Sialylated Glycans
Glycan-Binding Proteins
Specific Targeting of Cancer Cells
Antibody-Drug Conjugates
Nanoparticles
Sweetening Precision Oncology with Glycan-Directed Nanoparticles
Nanoparticle Strategies Using Glycoproteins
Glycan-Targeting Nanoparticles
Nanoparticles Strategies Using Glycan-Binding Proteins
Future Perspectives
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