TY - JOUR T1 - 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 JF - Anticancer Research JO - Anticancer Res SP - 4667 LP - 4671 DO - 10.21873/anticanres.13648 VL - 39 IS - 9 AU - HIROMICHI OSHIRO AU - YASUNORI TOME AU - TASUKU KIYUNA AU - SANG NAM YOON AU - THINZAR M. LWIN AU - QINGHONG HAN AU - YUYING TAN AU - KENTARO MIYAKE AU - TAKASHI HIGUCHI AU - NORIHIKO SUGISAWA AU - YUKI KATSUYA AU - JUN HO PARK AU - ZHIYING ZANG AU - SAHAR RAZMJOOEI AU - MICHAEL BOUVET AU - BRYAN CLARY AU - SHREE RAM SINGH AU - FUMINORI KANAYA AU - KOTARO NISHIDA AU - ROBERT M. HOFFMAN Y1 - 2019/09/01 UR - http://ar.iiarjournals.org/content/39/9/4667.abstract N2 - 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. ER -