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/G2 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 α-deamino-γ-mercaptomethane lyase [EC 184.108.40.206]). 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/G2 by methioninase treatment and then treated with chemotherapeutic agents active against cells in S/G2.
Keywords: Escherichia coli; PEGylation; S/G2; cancer; combination chemotherapy; gene cloning; methioninase; methionine dependence; purification; recombinant rMETase; selective cancer-cell-cycle arrest; trap.