4.7 Review

Abnormal saccharides affecting cancer multi-drug resistance (MDR) and the reversal strategies

Journal

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
Volume 220, Issue -, Pages -

Publisher

ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2021.113487

Keywords

Cancer chemotherapy; Saccharide abnormality; Multi-drug resistance (MDR); Reversal strategy

Funding

  1. National Natural Science Foundation of China [21772028]
  2. General Scientific Research Project of Guangzhou [201804010325]
  3. Chinese National Major Project for New Drug Innovation [2019ZX09201-002]

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Chemotherapy is the main treatment for multiple cancers, but cancer cells can develop multi-drug resistance (MDR) due to abnormalities in saccharides. Various reversal strategies have been proposed to overcome MDR, including depletion of ATP, combination therapy with traditional cytotoxic agents, and direct modification of the sugar moiety. Abnormal saccharides significantly impact cancer MDR development and provide a new perspective for improving chemotherapy outcomes.
Clinically, chemotherapy is the mainstay in the treatment of multiple cancers. However, highly adaptable and activated survival signaling pathways of cancer cells readily emerge after long exposure to chemotherapeutics drugs, resulting in multi-drug resistance (MDR) and treatment failure. Recently, growing evidences indicate that the molecular action mechanisms of cancer MDR are closely associated with abnormalities in saccharides. In this review, saccharides affecting cancer MDR development are elaborated and analyzed in terms of aberrant aerobic glycolysis and its related enzymes, abnormal glycan structures and their associated enzymes, and glycoproteins. The reversal strategies including depletion of ATP, circumventing the original MDR pathway, activation by or inhibition of sugar-related enzymes, combination therapy with traditional cytotoxic agents, and direct modification on the sugar moiety, are ultimately proposed. It follows that abnormal saccharides have a significant effect on cancer MDR development, providing a new perspective for overcoming MDR and improving the outcome of chemotherapy. (C) 2021 Elsevier Masson SAS. All rights reserved.

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