[HTML][HTML] Clinical development of metabolic inhibitors for oncology

KM Lemberg, SS Gori, T Tsukamoto… - The Journal of …, 2022 - Am Soc Clin Investig
The Journal of clinical investigation, 2022Am Soc Clin Investig
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 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.
The Journal of Clinical Investigation