Clinical development of metabolic inhibitors for oncology

Metabolic inhibitors have been used in oncology for decades, dating back to antimetabolites developed in the 1940s. In the past 25 years, there has been increased recognition of metabolic derangements in tumor cells leading to a resurgence of interest in targeting metabolism. More recently there has been recognition that drugs targeting tumor metabolism also affect the often acidic, hypoxic, immunosuppressive tumor microenvironment (TME) and non-tumor cell populations within it, including immune cells. Here we review small-molecule metabolic inhibitors currently in clinical development for oncology applications. For each agent, we evaluate the preclinical studies demonstrating antitumor and TME effects and review ongoing clinical trials. The goal of this Review is to provide an overview of the landscape of metabolic inhibitors in clinical development for oncology.

Automated summary

Metabolic inhibitors have been used in oncology for many years and have gained increased recognition recently. These drugs not only target tumor cells, but also have effects on the tumor microenvironment and immune cells. This review provides an overview of small-molecule metabolic inhibitors currently in clinical development for oncology, evaluating their antitumor and microenvironment effects based on preclinical studies and ongoing clinical trials.