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

Abstract

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.

Keywords: PDOX; TNBC; ascites; liver metastasis; lymph node; oral recombinant methioninase; patient-derived orthotopic xenograft; re-metastasis; treatment; triple-negative breast cancer.