As the result of recent advances in the study of cancer biology, new
hallmarks of cancer have emerged, including the reprogramming of energy metabolism.
Indeed, it has been shown that cancer cells adjust their metabolism towards a high
dependence on glycolysis for both energy and biosynthetic intermediate production. As
a result of their high glycolytic rates, cancer cells produce high amounts of lactate as an
end product. Therefore, to maintain their adapted metabolic phenotype, cancer cells, in
addition to upregulating glucose transporters and other proteins involved in the
glycolytic pathway, must also upregulate lactate transporters. In this context,
monocarboxylate transporter isoforms 1 and 4 (MCT1 and MCT4) have emerged as
important players in the maintenance of metabolic reprogramming of cancer cells: on
one hand, they mediate lactate efflux from cancer cells, facilitating the maintenance of
high glycolytic rates, and on the other hand, they also aid in the regulation of
intracellular pH via a proton symport mechanism. Thus, MCTs appear to be promising
targets in cancer therapy, especially in cancers with a hyperglycolytic and acid-resistant
phenotype. Indeed, some in vitro and in vivo studies targeting MCT expression or
function support the use of MCTs as therapeutic targets, and an MCT1-specific
inhibitor developed by AstraZeneca is currently in clinical trials.
After an introductory section describing the metabolic reprogramming of cancer cells,
this chapter will provide an up-to-date comprehensive review of recent achievements
concerning the exploitation of MCTs as targets for anti-cancer therapy.
Keywords: Cancer, CD147, FDG-PET, Glucose metabolism,
Immunohistochemistry, In vitro studies, In vivo studies, Lactate, Metabolic
reprogramming, Monocarboxylate transporters, Therapeutic targets, Warburg effect.
