Targeting glycolysis for cancer therapy using drug delivery systems

There is close crosstalk between cancer metabolism and immunity. Cancer metabolism regulation is a promising therapeutic target for cancer immunotherapy. Warburg effect is characterized by abnormal glucose metabolism that includes common features of increased glucose uptake and lactate production. The aerobic glycolysis can reprogram the cancer cells and promote the formation of a suppressive immune microenvironment. As a case in point, lactate plays an essential role in tumorigenesis, which is the end product of glycolysis as well as serves as a fuel supporting cancer cell survival. Meanwhile, it is also an important immune regulator that drives immunosuppression in tumors. Immunometabolic therapy is to intervene tumor metabolism and regulate the related metabolites that participate in the innate and acquired immunity, thereby reinstalling the immune balance and eliciting anticancer immune responses. In this contribution to the Orations - New Horizons of the Journal of controlled Release I will provide an overview of glucose metabolism in tumors and its effects on drug resistance and tumor metastasis, and present the advance of glycolysis-targeting therapy strategies with drug delivery techniques, as well as discuss the challenges in glycolysis-targeting immunometabolic therapy.