Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Oncology Therapeutics Targeting the Metabolism of Amino Acids

Version 1 : Received: 27 July 2020 / Approved: 29 July 2020 / Online: 29 July 2020 (12:35:37 CEST)

A peer-reviewed article of this Preprint also exists.

Muhammad, N.; Lee, H.M.; Kim, J. Oncology Therapeutics Targeting the Metabolism of Amino Acids. Cells 2020, 9, 1904. Muhammad, N.; Lee, H.M.; Kim, J. Oncology Therapeutics Targeting the Metabolism of Amino Acids. Cells 2020, 9, 1904.

Abstract

Amino acid metabolism promotes cancer cell proliferation and survival by supporting building block synthesis, producing reducing agents to mitigate oxidative stress, and generating immunosuppressive metabolites for immune evasion. Malignant cells rewire amino acid metabolism to maximize their access to nutrients. Amino acid transporter expression is upregulated to acquire amino acids from the extracellular environment. Under nutrient depleted conditions, macropinocytosis can be activated where proteins from the extracellular environment are engulfed and degraded into the constituent amino acids. The demand for non-essential amino acids (NEAAs) can be met through de novo synthesis pathways. Cancer cells can alter various signaling pathways to boost amino acid usage for the generation of nucleotides, reactive oxygen species (ROS) scavenging molecules and oncometabolites. The importance of amino acid metabolism in cancer proliferation makes it a potential target for therapeutic intervention, including via small molecules and antibodies. In this review, we will delineate the targets related to amino acid metabolism and promising therapeutic approaches.

Keywords

cancer metabolism; amino acids; oncogenic therapeutics

Subject

Medicine and Pharmacology, Oncology and Oncogenics

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