Inhibition of Cancer Metabolism: a Patent Landscape

Abstract

Cancer metabolism is currently a hot topic. Since it was first realized that cancer cells rely upon an altered metabolic program to sustain their rapid proliferation, the enzymes that support those metabolic changes have appeared to be good targets for pharmacological intervention. Here, we discuss efforts pertaining to targets in cancer metabolism, focusing upon the tricarboxylic acid cycle and the mechanisms which feed nutrients into it. We describe a broad landscape of small-molecule inhibitors, targeting a dozen different proteins, each implicated in cancer progression. We hope that this will serve as a reference both to the areas being most highly examined today and, relatedly, the areas that are still ripe for novel intervention.

Lactate dehydrogenase: a marker of diminished antitumor immunity

“…Although glycolysis inhibitors have not yet been approved in clinical practice, several glycolysis inhibitors have been developed and are currently being evaluated in preclinical and early clinical trials. 60,61 Given the negative effects of glycolysis on antitumor immunity, there is a clear rationale for combining checkpoint inhibitors with glycolysis inhibitors. Yet, there are concerns regarding the effect of glycolysis inhibitors on T cells, because T cells depend on glycolysis for their function.…”