Response of Triple-negative Breast Cancer Liver Metastasis to Oral Recombinant Methioninase in a Patient-derived Orthotopic Xenograft (PDOX) Model.

BACKGROUND/AIM: The aim of this study was to establish a patient-derived orthotopic xenograft (PDOX) mouse model of liver metastasis of triple-negative breast cancer (TNBC) and examine the efficacy of oral recombinant methioninase (o-rMETase) on the liver metastasis. MATERIALS AND METHODS: TNBC from a patient was implanted in the left hepatic lobe of nude mice to simulate liver metastasis in a PDOX model. Ten days later, all mice underwent laparotomy to measure tumor size and were randomized to three groups: control; o-rMETase 100 U once daily (qd); and o-rMETase 200 U qd. After 9 days of treatment, all mice were sacrificed. RESULTS: At the end of the treatment period for the liver metastasis, the size of liver metastases was 372.6 mm3 in the control group; 160.0 mm3 in the o-rMETase 100 U group; and 245.3 mm3 in the o-rMETase 200 U group. All mice had ascites and 12 out of 14 mice in all groups had mesenteric lymph-node metastasis, as re-metastasis. The mean body-condition score was 1.5 in the control group; 2.4 in the o-rMETase 100 U group; and 2.6 in the o-rMETase 200 U group (control group vs. o-rMETase 200 U group, p<0.05). CONCLUSION: The TNBC liver metastasis was highly aggressive resulting in re-metastasis and ascites. o-rMETase tended to inhibit the liver metastasis and significantly improved the mouse body-condition score. This new PDOX model of TNBC liver metastasis will be useful for identifying effective agents for this recalcitrant disease.

Oral Methioninase Inhibits Recurrence in a PDOX Mouse Model of Aggressive Triple-negative Breast Cancer.

BACKGROUND/AIM: The aim of the study was to use a triple-negative breast cancer (TNBC) patient-derived orthotopic xenograft (PDOX) model to examine the efficacy of oral recombinant methioninase (o-rMETase) against this recalcitrant disease. MATERIALS AND METHODS: The TNBC tumor from a patient was implanted in the right 4th inguinal mammary fat pad of nude mice. Two weeks later, the mice underwent tumorectomy with grossly-negative surgical margins. Two days after tumorectomy the mice were divided in two groups: one control and one treated with o-rMETase. RESULTS: Tumors recurred in all mice. On day 11, the mean recurrent tumor volumes were 936.7 mm3 in the control group and 450.9 mm3 in the o-rMETase group (p<0.05). On day 15, the mean recurrent tumor volumes were 3392.5 mm3 in the control group and 1603.5 mm3 in the o-rMETase group. The mean recurrent tumor weights were 2.1 g in the control group and 1.1 g in the o-rMETase group on day 15. CONCLUSION: o-rMETase is an effective adjuvant treatment for aggressive TNBC.