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Pharmacological development of glycosylation-directed anticancer interventions: Target engagement, pharmacodynamics and therapeutic index.

Created on 11 Sep 2026

Authors

Xing Jin, Jiakang Ma, Hongqiao Hou, Xiusen Zhang, Xudong Zhang, Shilei Zhang, Hairui Wang, Xin Zhao, Guangping Zhang

Published in

Biochemical pharmacology. Pages 118460. Sep 10, 2026. Epub Sep 10, 2026.

Abstract

Glycosylation-dependent processes influence protein maturation, cell-surface receptor organisation, immune recognition and adaptation to treatment-induced stress, making them potential targets for anticancer intervention. Yet evidence that a glycosylation-related event contributes to tumour growth or drug resistance does not establish that pharmacological intervention will be effective, selective or clinically tractable. This review examines the evidence needed to develop glycosylation-directed anticancer interventions, including intracellular enzyme and pathway inhibitors, targeted glycan-editing strategies, glycoform-selective biologics and agents that disrupt glycan-lectin interactions. We focus on the relationship between systemic and intratumoural exposure, direct tumour target engagement, mechanism-proximal pharmacodynamic effects, downstream functional consequences and normal-tissue pharmacology. Particular attention is given to distinguishing intended target modulation from generalised endoplasmic-reticulum stress, metabolic perturbation, immune activation or non-specific cytotoxicity. We also consider how these principles should guide dose and schedule selection, paired tumour-biopsy studies, mechanism-based combination development and go/no-go decisions in early clinical trials. Glycosylation-directed interventions should advance only when meaningful tumour modulation can be demonstrated at an exposure compatible with an acceptable therapeutic index.

PMID:
42722084
Bibliographic data and abstract were imported from PubMed on 11 Sep 2026.

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