Glutaminase regulation in cancer cells: a druggable chain of events

• Inhibition of glutamine metabolism is an important mechanism in cancer control.
• Novel drugs offer a mechanism by which the key metabolic enzyme glutaminase might be inhibited.
• Regulators of glutaminase offer additional opportunities for modulating cancer metabolism.

Metabolism is the process by which cells convert relatively simple extracellular nutrients into energy and building blocks necessary for their growth and survival. In cancer cells, metabolism is dramatically altered compared with normal cells. These alterations are known as the Warburg effect. One consequence of these changes is cellular addiction to glutamine. Because of this, in recent years the enzyme glutaminase has become a key target for small molecule therapeutic intervention. Like many oncotargets, however, glutaminase has a number of upstream partners that might offer additional druggable targets. This review summarizes the work from the current decade surrounding glutaminase and its regulation, and suggests strategies for therapeutic intervention in relevant cases.