High Efficacy of Recombinant Methioninase on Patient-Derived Orthotopic Xenograft (PDOX) Mouse Models of Cancer

  • Robert M. HoffmanEmail author
  • Takashi Murakami
  • Kei Kawaguchi
  • Kentaro Igarashi
  • Yuying Tan
  • Shukuan Li
  • Qinghong Han
Part of the Methods in Molecular Biology book series (MIMB, volume 1866)


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.

Key words

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


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Robert M. Hoffman
    • 1
    • 2
    Email author
  • Takashi Murakami
    • 1
    • 2
  • Kei Kawaguchi
    • 1
    • 2
  • Kentaro Igarashi
    • 1
    • 2
  • Yuying Tan
    • 1
  • Shukuan Li
    • 1
  • Qinghong Han
    • 1
  1. 1.AntiCancer, Inc.San DiegoUSA
  2. 2.Department of SurgeryUniversity of CaliforniaSan DiegoUSA

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