title: Development of recombinant methioninase to target the general cancer-specific metabolic defect of methionine dependence: a 40-year odyssey.
abstract: BACKGROUND
  All tested cancer cell types are methionine dependent in that the cells arrest and eventually die when deprived of methionine, a condition that is generally nontoxic to normal cells. Methionine dependence is the only known general metabolic defect in cancer. Methionine-deprived cancer cells arrest at the S/G2 phase, an unusual position for cell cycle arrest. In order to exploit the cancer-specific metabolic defect of methionine dependence, methioninases were developed.
  
  
  METHODS
  The present Expert Opinion describes the phenomena of methionine dependence and a methioninase cloned from Pseudomonas putida (chemical name: l-methionine α-deamino-γ-mercaptomethane lyase [EC 4.4.1.11]). The cloned methioninase, termed recombinant methioninase, or rMETase, has been tested in mouse models of human cancer as well as in macaque monkeys and a pilot Phase I trial of human cancer patients. Efficacy of rMETase has been demonstrated against various cancer types in mouse models.
  
  
  CONCLUSIONS
  The most promising application of rMETase therapy is in sequential combination therapy, whereby the cancer cells within a tumor are trapped in S/G2 by methioninase treatment and then treated with chemotherapeutic agents active against cells in S/G2.
authors.affiliation: AntiCancer, Inc. , 7917 Ostrow Street, San Diego, CA 92111 , USA +1 858 654 2555 ; +1 858 268 4175 ; all@anticancer.com.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Hoffman
mesh_terms: D000818:Animals; D013437:Carbon-Sulfur Lyases / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D017321:Clinical Trials, Phase I as Topic; D003001:Cloning, Molecular; D003131:Combined Modality Therapy; D006801:Humans; D008251:Macaca; D008715:Methionine / Q000378:metabolism*; D051379:Mice; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D016958:Pseudomonas putida / Q000201:enzymology / Q000235:genetics; D011994:Recombinant Proteins / Q000627:therapeutic use*
chemical_list: D011994:Recombinant Proteins; D008715:Methionine; D013437:Carbon-Sulfur Lyases; C021558:L-methionine gamma-lyase
keywords: Escherichia coli; PEGylation; S/G2; cancer; combination chemotherapy; gene cloning; methioninase; methionine dependence; purification; recombinant rMETase; selective cancer-cell-cycle arrest; trap