Oral Recombinant Methioninase Overcomes Colorectal-cancer Liver Metastasis Resistance to the Combination of 5-Fluorouracil and Oxaliplatinum in a Patient-derived Orthotopic Xenograft Mouse Model.

Abstract

BACKGROUND/AIM:

Liver metastasis in colorectal-cancer is a recalcitrant disease. To develop precision individualized therapy of this disease, we developed a patient-derived orthotopic xenograft (PDOX) model of colorectal-cancer liver metastasis. In the present report, we evaluated the efficacy of oral recombinant methioninase (o-rMETase) in combination with 5-fluorouracil (5-FU) and oxaliplatinum (OXA) on the colorectal-cancer liver metastasis PDOX mouse model.

MATERIALS AND METHODS:

Colorectal-cancer liver metastasis PDOX models were randomized into three groups of seven mice. Group 1, untreated control with phosphate buffered saline (PBS); Group 2, treated with 5-FU + OXA; and Group 3, treated with 5-FU + OXA + o-rMETase.

RESULTS:

The colorectal-cancer liver metastasis PDOX model was resistant to 5-FU + OXA (p=0.83 at day 15 of treatment, Group 2). In contrast, the colorectal-cancer liver metastasis PDOX model was arrested by o-rMETase combined with 5-FU + OXA (p<0.01 at day 15, Group 3). No significant body-weight differences were observed among the groups.

CONCLUSION:

The combination therapy of 5-FU and OXA with o-rMETase can overcome the resistance of first line drugs for colorectal-cancer liver metastasis.

• Authors: Hiromichi Oshiro, Yasunori Tome, Tasuku Kiyuna, Sang Nam Yoon, Thinzar M Lwin, Qinghong Han, Yuying Tan, Kentaro Miyake, Takashi Higuchi, Norihiko Sugisawa, Yuki Katsuya, Jun Ho Park, Zhiying Zang, Sahar Razmjooei, Michael Bouvet, Bryan Clary, Shree Ram Singh, Fuminori Kanaya, Kotaro Nishida, Robert M Hoffman
• Journal: Anticancer research (Anticancer Res) Vol. 39 Issue 9 Pg. 4667-4671 (Sep 2019) ISSN: 1791-7530 [Electronic] Greece
• PMID: 31519565 (Publication Type: Journal Article)
• Copyright: Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Chemical References

• Antimetabolites, Antineoplastic
• Oxaliplatin
• Carbon-Sulfur Lyases
• L-methionine gamma-lyase
• Fluorouracil

Topics

• Animals
• Antimetabolites, Antineoplastic (administration & dosage)
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Carbon-Sulfur Lyases (administration & dosage)
• Colorectal Neoplasms (drug therapy, pathology)
• Disease Models, Animal
• Fluorouracil (administration & dosage)
• Humans
• Liver Neoplasms (drug therapy, pathology, secondary)
• Mice
• Oxaliplatin (administration & dosage)
• Xenograft Model Antitumor Assays