Lactate transporters as therapeutic targets in cancer and inflammatory diseases

Abstract

Inflammation is associated with the accumulation of lactate at sites of tumor-growth and inflammation. Lactate initiates tissue-responses contributing to disease. We discuss the potential of targeting lactate transporters in the treatment of cancer and inflammatory conditions. Areas covered: Lactate is the end product of glycolysis, often considered a waste metabolite but also a fuel for oxidative cells. It is however an active signaling molecule with immunomodulatory and angiogenic properties. They are the consequence of lactate binding to membrane receptor(s) or being transported through specific carrier-mediated-transporters across the cellular membrane. Carriers are distinct in proton-linked-monocarboxylate-transporters (MCTs) and Na⁺-coupled- electrogenic-transporters, expressed by several tissues including immune-system, endothelium and epithelium. Several tumors and inflammatory sites show accumulation of lactate and altered expression of its transporters, thus suggesting a role of this metabolite in cancer and inflammation. We review the most recent evidence on lactate biology, focusing on transporter expression and function in health and disease. Expert opinion: Lactate-initiated signaling is gaining attention for its implications in cancer and inflammation. This review discusses the therapeutic potential of targeting lactate transporters and drugs that are already in clinical use for cancer and discusses the opportunity to develop new therapeutics for inflammation and cancer.

Keywords: Lactate; cancer; immunity; inflammation; lactate transporter; metabolism.