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Clinical development of metabolic inhibitors for oncology
Kathryn M. Lemberg, … , Rana Rais, Barbara S. Slusher
Kathryn M. Lemberg, … , Rana Rais, Barbara S. Slusher
Published January 4, 2022
Citation Information: J Clin Invest. 2022;132(1):e148550. https://doi.org/10.1172/JCI148550.
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Review Series

Clinical development of metabolic inhibitors for oncology

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Abstract

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.

Authors

Kathryn M. Lemberg, Sadakatali S. Gori, Takashi Tsukamoto, Rana Rais, Barbara S. Slusher

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Figure 1

Metabolic inhibitors under clinical investigation for oncology applications.

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Metabolic inhibitors under clinical investigation for oncology applicati...
Schematic depicts the metabolic pathways and processes inhibited by agents described in this Review. Agents are shown in red text. Key enzymes are shown in pink. Pathways are labeled in yellow. Metabolites are shown in blue.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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