Abnormal saccharides affecting cancer multi-drug resistance (MDR) and the reversal strategies
Meizhu Wang1, Wenming Chen2, Jiansheng Chen3
1School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, E. 232, University Town, Waihuan Rd, Panyu, Guangzhou, 510006, China; Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, 200241, Shanghai, China.
Abstract:
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.
Insights
Cancer cells develop multi-drug resistance (MDR) through abnormal saccharide metabolism. Targeting these sugar-related pathways offers new strategies to overcome chemotherapy resistance and improve cancer treatment outcomes.
Area of Science:
- Biochemistry
- Oncology
- Cancer Biology
Background:
- Chemotherapy is a primary cancer treatment, but drug resistance limits its effectiveness.
- Cancer cells develop multi-drug resistance (MDR) via adaptable survival pathways.
- Emerging evidence links cancer MDR to aberrant saccharide metabolism and structures.
Purpose of the Study:
- To review the role of saccharides in cancer MDR development.
- To analyze molecular mechanisms involving aberrant glycolysis, glycan structures, and glycoproteins.
- To propose novel strategies for overcoming MDR.
Main Methods:
- Literature review focusing on saccharide involvement in cancer MDR.
- Analysis of aberrant aerobic glycolysis and related enzymes.
- Examination of abnormal glycan structures and associated enzymes.
- Investigation of glycoprotein alterations in MDR.
Main Results:
- Abnormalities in aerobic glycolysis, glycan structures, and glycoproteins contribute to cancer MDR.
- Specific enzymes and molecular pathways involving saccharides are implicated in resistance.
- Saccharide modifications represent a key factor in MDR development.
Conclusions:
- Abnormal saccharide metabolism and structures are significant drivers of cancer MDR.
- Targeting sugar-related pathways presents a promising approach to enhance chemotherapy efficacy.
- Developing strategies focused on saccharide moieties can overcome MDR and improve patient outcomes.
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