High efficacy of recombinant methioninase on patient-derived orthotopic xenograft (PDOX) mouse models of cancer

Robert M. Hoffman, Takashi Murakami, Kei Kawaguchi, Kentaro Igarashi, Yuying Tan, Shukuan Li, Qinghong Han

Research output: Chapter in Book/Report/Conference proceedingChapter

3 Citations (Scopus)

Abstract

Methionine (MET) is a general target in cancer due to the excess requirement of MET by cancer cells. MET has been effectively restricted by recombinant methioninase (rMETase) in mouse models of cell-line tumors. This chapter reviews the efficacy of rMETase on patient-derived orthotopic xenograft (PDOX) mouse models of human cancer. Ewing’s sarcoma is a recalcitrant disease even though development of multimodal therapy has improved patients’ outcome. A Ewing’s sarcoma was implanted in the right chest wall of nude mice to establish a PDOX model. rMETase effectively reduced tumor growth compared to the untreated control. The MET level both of plasma and supernatants derived from sonicated tumors was lower in the rMETase treatment group. Body weight did not significantly differ at any time points between the two groups. A PDOX nude mouse model of a BRAF V600E-mutant melanoma was established in the chest wall of nude mice and also tested with rMETase in combination with a first-line melanoma drug, temozolomide (TEM). Combination therapy of TEM and rMETase was significantly more efficacious than either monotherapy. The results reviewed in this chapter demonstrate the clinical potential of rMETase.

Original languageEnglish
Title of host publicationMethods in Molecular Biology
PublisherHumana Press Inc.
Pages149-161
Number of pages13
DOIs
Publication statusPublished - 2019
Externally publishedYes

Publication series

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

Keywords

  • Chemotherapy
  • Combination
  • Methionine dependence
  • PDOX
  • Patient-derived orthotopic xenograft
  • Recombinant methioninase
  • rMETase

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics

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