The Typical Metabolic Modifiers Conferring Improvement in Cancer Resistance

Abstract

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 criteria.

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 systematically.

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 exerting synergism.

Keywords: 2-deoxy-Dglucose; 3-bromopyruvate.; Cancer resistance; cancer metabolic reprogramming; lonidamine; metabolic modifiers.