Background: Cancer metabolic reprogramming rekindles enthusiasm for the research
of metabolic regulation in cancer drug resistance. A growing number of metabolic
modifiers combined with cancer drugs obtain the expected efficacy in in vitro or in vivo studies,
also in clinical trial studies, indicating a good potential of enhancing efficacy and reducing
resistance. Hence, a comprehensive review on the attenuations of metabolic modifiers in
cancer drug resistance is necessary for rational drug design and clinical cancer drug research.
Methods: Cancer drug resistance and cancer metabolic reprogramming were used as the key
words to collect publications with reference value in bibliographic databases. Specifically, the
focused question is the advances of metabolic modifiers on cancer resistance improvement.
Figures and tables were applied to analyze the interventions in accordance with the inclusion
Results: This review summarized the advances of metabolic modifiers combined with cancer
drugs in in vitro, in vivo and clinical trial studies, especially for cancer resistance improvement.
The relationship between metabolic regulation and cancer resistance was elaborated,
and the potential metabolic modifiers were embraced. Metabolic targets were also visualized
in categorization in 4 figures and expatiated in 4 tables. Three typical metabolic modifiers,
namely lonidamine, 2-DG and 3-BrPA, conferring attenuation to cancer resistance were elucidated
Conclusion: Metabolic regulation is an intervention with targeted perturbation in a modest
manner and reflects homeostasis balance. When combined with cancer drugs, the metabolic
modifiers always show exciting potential with practical significance, enhancing activity or