Glyco‐nano‐oncology: Novel Therapeutic Opportunities by Combining Small and Sweet

P. F HOCKL; A. WOLOSIUK; J. M. PÉREZ SÁEZ; A. BORDONI; D. O. CROCI; Y. TOUM; G. J. A. A. SOLER-ILLIA; G. A. RABINOVICH

PHARMACOLOGICAL RESEARCH

ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD

Lugar: Amsterdam; Año: 2016 vol. 109 p. 45 - 54

1043-6618

Recent efforts toward defining the molecular features of the tumor microenvironment have revealed dramatic changes in the expression of glycan-related genes including glycosyltransferases and glycosidases. These changes affect glycosylation of proteins and lipids not only in cancer cells themselves, but also in cancer associated-stromal, endothelial and immune cells. These glycan alterations including increased frequency of β1,6-branched N-glycans and bisecting N-glycans, overexpression of tumor-associated mucins, preferred expression of T, Tn and sialyl-Tn antigen and altered surface sialylation, may contribute to tumor progression by masking or unmasking specific ligands for endogenous lectins, including members of the C-type lectin, siglec and galectin families. Differential expression of glycans or glycan-binding proteins could be capitalized for the identification of novel biomarkers and might provide novel opportunities for therapeutic intervention. This review focuses on the biological relevance of lectin-glycan interactions in the tumor microenvironment (mainly illustrated by the immunosuppressive and pro-angiogenic activities of galectin-1) and the design of functionalized nanoparticles for pharmacological delivery of multimeric glycans, lectins or selective inhibitors of lectin-glycan interactions with antitumor activity.