Journal
EXPERT OPINION ON BIOLOGICAL THERAPY
Volume 15, Issue 1, Pages 21-31Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1517/14712598.2015.963050
Keywords
cancer; combination chemotherapy; Escherichia coli; gene cloning; methioninase; recombinant rMETase; methionine dependence; PEGylation; purification; S/G(2); selective cancer-cell-cycle arrest; trap
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Introduction: 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/G(2) phase, an unusual position for cell cycle arrest. In order to exploit the cancer-specific metabolic defect of methionine dependence, methioninases were developed. Areas covered: The present Expert Opinion describes the phenomena of methionine dependence and a methioninase cloned from Pseudomonas putida (chemical name: L-methionine alpha-deamino-gamma-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. Expert opinion: The most promising application of rMETase therapy is in sequential combination therapy, whereby the cancer cells within a tumor are trapped in S/G(2) by methioninase treatment and then treated with chemotherapeutic agents active against cells in S/G(2).
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