Progress in Clinical Application of Monocarboxylate Trans-porters in Tumors
Tumor cells exhibit high rates of glycolysis due to the presence of metabolic repro-gramming,resulting in excessive lactate production as well as increased extracellular acidity.Pro-ton-linked monocarboxylate transporter(MCT)are essential for maintaining this metabolic pheno-type by mediating proton-coupled lactate transport across cell membranes and also contribute to tumor cell pH regulation.Among the proteins encoded by the SLC16 gene family,the MCT1 and MCT4 subtypes are the most studied in tumors,and they are overexpressed in a variety of tumor types,such as solid tumors and hematologic malignancies.Similar to what occurs in specific physiological environments,MCT1 and MCT4 are able to mediate lactate shuttling between tumor cells and between tumor and stromal cells in the tumor microenvironment.This form of metabolic cooperative mode is responsible for important tumor aggressive features,including cell prolifera-tion,survival,angiogenesis,migration,invasion,metastasis,immune tolerance,and treatment resistance.The growing understanding of the functional regulation of MCTs provides a new avenue for the design of novel inhibitors that are foreseeable in clinical practice.This review provides an overview of the role of MCT subtypes in tumors,summarizes recent advances in their pharmaco-logical targeting,and summarizes the potential of novel potent and selective MCT1 and/or MCT4 inhibitors in cancer therapy.
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