The combination of oral-recombinant methioninase and azacitidine arrests a chemotherapy-resistant osteosarcoma patient-derived orthotopic xenograft mouse model.

Abstract

PURPOSE:

Cancers are methionine (MET) and methylation addicted, causing them to be highly sensitive to MET restriction. The present study determined the efficacy of restricting MET with oral-recombinant methioninase (o-rMETase) and the DNA methylation inhibitor, azacitidine (AZA) on a chemotherapy-resistant osteosarcoma patient-derived orthotopic xenograft (PDOX) mouse model.

METHODS:

The osteosarcoma PDOX models were randomized into five treatment groups of six mice: control; doxorubicin (DOX) alone; AZA alone; o-rMETase alone; o-rMETase-AZA combination. Tumor size and body weight were measured during the 14 days of treatment.

RESULTS:

We found that tumor growth was arrested only by the o-rMETase-AZA combination treatment, as tumors with this treatment exhibited tumor necrosis with degenerative change.

CONCLUSION:

This study suggests that o-rMETase-AZA combination has clinical potential for patients with chemoresistant osteosarcoma.

• Authors: Takashi Higuchi, Norihiko Sugisawa, Jun Yamamoto, Hiromichi Oshiro, Qinghong Han, Norio Yamamoto, Katsuhiro Hayashi, Hiroaki Kimura, Shinji Miwa, Kentaro Igarashi, Yuying Tan, Shreya Kuchipudi, Michael Bouvet, Shree Ram Singh, Hiroyuki Tsuchiya, Robert M Hoffman
• Journal: Cancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 85 Issue 2 Pg. 285-291 (02 2020) ISSN: 1432-0843 [Electronic] Germany
• PMID: 31705268 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Doxorubicin
• Carbon-Sulfur Lyases
• L-methionine gamma-lyase
• Azacitidine

Topics

• Adolescent
• Animals
• Antineoplastic Agents (pharmacology, therapeutic use)
• Azacitidine (pharmacology)
• Bone Neoplasms (drug therapy)
• Carbon-Sulfur Lyases (pharmacology)
• Combined Modality Therapy (methods)
• Disease Models, Animal
• Doxorubicin (pharmacology)
• Drug Resistance, Neoplasm (drug effects)
• Heterografts (drug effects)
• Humans
• Male
• Mice
• Mice, Nude
• Osteosarcoma (drug therapy)
• Tumor Burden (drug effects)
• Xenograft Model Antitumor Assays (methods)