Lactate Dehydrogenase Inhibition: Exploring Possible Applications Beyond Cancer Treatment

Abstract

Lactate dehydrogenase (LDH) inhibition is considered a worthwhile attempt in the development of innovative anticancer strategies. Unfortunately, in spite of the involvement of several research institutions and pharma-companies, the discovery of LDH inhibitors with drug-like properties seems a hardly resolvable challenge. While awaiting new advancements, in the present review we will examine other pathologic conditions characterized by increased glycolysis and LDH activity, which could potentially benefit from LDH inhibition. The rationale for targeting LDH activity in these contexts is the same justifying the LDH-based approach in anticancer therapy: because of the enzyme position at the end of glycolytic pathway, LDH inhibitors are not expected to hinder glucose metabolism of normal cells. Moreover, we will summarize the latest contributions in the discovery of enzyme inhibitors and try to glance over the reasons underlying the complexity of this research.

Vitamin K: Redox-modulation, prevention of mitochondrial dysfunction and anticancer effect

“…Cancer cells are characterized by high levels of glucose, anaerobic oxidation of glucose (Warburg effect) and accumulation of lactate, compared to normal cells [43] , [44] , [48] , [79] . In last years, lactate dehydrogenase is receiving a great deal of attention as a potential diagnostic marker or a predictive biomarker for many types of cancer and as a therapeutic target for development of new anticancer drugs [80] , [81] , [82] .…”

When Will Small Molecule Lactate Dehydrogenase Inhibitors Realize Their Potential in the Cancer Clinic?

“…The NAD (+) thus obtained to determine the continuity of glycolysis [4]. Till date, the hLDH-5 isoform received a position in the list of highly promising hallmark of cancer, in other words, highly promising targets for cancer drug development and cancer treatment due to following main crucial facts such as: hLDH-5 isoform holds significant role as a metabolic checkpoint in the cancer glycolytic pathway; associations of this enzyme with the activation of some proto-oncogenes; its link with the maintenance of invasiveness and metastatic potential; and finally connection of hLDH-5 isoform to chemoresistance of cancer cells [5,6]. …”

Tumour biomarkers: homeostasis as a novel prognostic indicator

“…The lactate dehydrogenase-A that catalyses the inter-conversion of pyruvate and lactate is the main enzyme responsible for the Warburg effect, thus it is upregulated in human cancers and associated with aggressive tumour outcomes [141]. Therefore, in cancer, many studies have targeted the glycolytic pathway, and in particular LDH enzyme, with the aim to develop or to screen new innovative anti-cancer strategies [142,143]. …”