title: Molecular basis and current strategies of therapeutic arginine depletion for cancer.
abstract: Renewed interest in the use of therapeutic enzymes combined with an improved knowledge of cancer cell metabolism, has led to the translation of several arginine depletion strategies into early phase clinical trials. Arginine auxotrophic tumors are reliant on extracellular arginine, due to the downregulation of arginosuccinate synthetase or ornithine transcarbamylase-key enzymes for intracellular arginine recycling. Engineered arginine catabolic enzymes such as recombinant human arginase (rh-Arg1-PEG) and arginine deiminase (ADI-PEG) have demonstrated cytotoxicity against arginine auxotrophic tumors. In this review, we discuss the molecular events triggered by extracellular arginine depletion that contribute to tumor cell death.
authors.affiliation: Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom.
authors.forename: Livingstone
authors.initials: L
authors.lastname: Fultang
authors.affiliation: Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom.
authors.forename: Ashley
authors.initials: A
authors.lastname: Vardon
authors.affiliation: Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom.
authors.forename: Carmela
authors.initials: C
authors.lastname: De Santo
authors.affiliation: Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom.
authors.forename: Francis
authors.initials: F
authors.lastname: Mussai
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001119:Arginase / Q000627:therapeutic use; D001120:Arginine / Q000378:metabolism*; D049109:Cell Proliferation; D002470:Cell Survival; D002986:Clinical Trials as Topic; D004353:Drug Evaluation, Preclinical; D057487:Enzyme Therapy / Q000379:methods; D006801:Humans; D006867:Hydrolases / Q000627:therapeutic use; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013312:Stress, Physiological / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D001120:Arginine; D006867:Hydrolases; D001119:Arginase; C019723:arginine deiminase
keywords: arginine deiminase; arginine deprivation; recombinant human arginase