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

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. The inner relationship of saccharides and multi-drug resistance (MDR) in cancer is systematically analyzed and summarized from three aspects: i) high-rate glycolysis and its associated enzymes; ii) abnormality in glycans and its related enzymes; iii) aberrant glycoproteins. Accordingly, the five reversal strategies are proposed, in hope to constitute a novel platform for eliminating MDR in cancer. [Display omitted] •Abnormality in saccharides usually drives cancer MDR (Multidrug Resistance) development.•The possible mechanisms of saccharide-mediated cancer MDR are systematically analyzed from three novel perspectives.•Five reversal strategies towards the mechanisms of cancer MDR development are proposed.