Plant-derived extracts and metabolic modulation in leukemia: a promising approach to overcome treatment resistance

Leukemic cells acquire complex and often multifactorial mechanisms of resistance to treatment, including various metabolic alterations. Although the use of metabolic modulators has been proposed for several decades, their use in clinical practice has not been established. Natural products, the so-called botanical drugs, are capable of regulating tumor metabolism, particularly in hematopoietic tumors, which could partly explain the biological activity attributed to them for a long time. This review addresses the most recent findings relating to metabolic reprogramming-Mainly in the glycolytic pathway and mitochondrial activity-Of leukemic cells and its role in the generation of resistance to conventional treatments, the modulation of the tumor microenvironment, and the evasion of immune response. In turn, it describes how the modulation of metabolism by plant-derived extracts can counteract resistance to chemotherapy in this tumor model and contribute to the activation of the antitumor immune system.

Automated summary

Leukemic cells develop resistance to treatment through complex and multifactorial mechanisms, including metabolic alterations. The use of metabolic modulators has been proposed for decades but has not been established in clinical practice. Natural products, particularly botanical drugs, can regulate tumor metabolism and counteract resistance to chemotherapy in hematopoietic tumors. This review discusses the recent findings on metabolic reprogramming in leukemic cells, its role in treatment resistance, modulation of the tumor microenvironment, and evasion of immune response, as well as how plant-derived extracts can modulate metabolism and activate the antitumor immune system.