Afterword: Oral methioninase—answer to cancer and fountain of youth?

Robert M. Hoffman, Qinghong Han, Kei Kawaguchi, Shukuan Li, Yuying Tan

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

The elevated methionine (MET) requirement of cancer cells is termed MET dependence and is possibly the only known general metabolic defect in cancer. Targeting MET by recombinant methioninase (rMETase) can arrest the growth of cancer cells in vitro and in vivo due to their elevated requirement for MET. rMETase can also potentiate chemotherapy drugs active in S phase due to the selective arrest of cancer cells in S/G2 phase during MET restriction (MR). We previously reported that rMETase, administrated by intraperitoneal injection (ip-rMETase), could inhibit tumor growth in mouse models of cancer including patient-derived orthotopic xenograft (PDOX) mouse models. We subsequently compared ip-rMETase and oral rMETase (o-rMETase) on a melanoma PDOX mouse model. o-rMETase was significantly more effective than ip-rMETase to inhibit tumor growth without overt toxicity. The combination of o-rMETase+ip-rMETase was significantly more effective than either monotherapy and completely arrested tumor growth. Thus, o-rMETase is effective as an anticancer agent with the potential of clinical development for chronic cancer therapy as well as for cancer prevention. o-rMETase may also have potential as an antiaging agent for healthy people, since MR has been shown to extend the life span of a variety of different organisms.

Original languageEnglish
Title of host publicationMethods in Molecular Biology
PublisherHumana Press Inc.
Pages311-322
Number of pages12
DOIs
Publication statusPublished - 2019 Jan 1
Externally publishedYes

Publication series

NameMethods in Molecular Biology
Volume1866
ISSN (Print)1064-3745

Keywords

  • Melanoma
  • Methionine dependence
  • Nude mice
  • Oral administration
  • Orthotopic
  • PDOX
  • Pyridoxal-l-phosphate
  • Recombinant methioninase

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics

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