Targeting amino acid metabolism in cancer growth and anti-tumor immune response

Abstract

Recent advances in amino acid metabolism have revealed that targeting amino acid metabolic enzymes in cancer therapy is a promising strategy for the development of novel therapeutic agents. There are currently several drugs in clinical trials that specifically target amino acid metabolic pathways in tumor cells. In the context of the tumor microenvironment, however, tumor cells form metabolic relationships with immune cells, and they often compete for common nutrients. Many tumors evolved to escape immune surveillance by taking advantage of their metabolic flexibility and redirecting nutrients for their own advantage. This review outlines the most recent advances in targeting amino acid metabolic pathways in cancer therapy while giving consideration to the impact these pathways may have on the anti-tumor immune response.

Keywords: Amino acid metabolism, T cells, Anti-tumor immune response, Tumor microenvironment, Cancer therapy

Core tip: Amino acid metabolism has been a focus of increased attention by cancer researchers and immunologists due to its importance for the metabolic reprogramming of proliferating cells. Many amino acid enzymes are described as immunosuppressive in the tumor microenvironment and targeted for cancer therapy. This review addresses the metabolic control of tumor progression in the context of anti-tumor immunity and discusses current and future therapeutic approaches. Special emphasis is given to the emerging role of branched chain amino acid metabolism in cancer and immunity highlighting some recent work by our research group.