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

Abstract

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 4^th 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.

Keywords: PDOX; Recombinant methioninase; TNBC; inhibitor; patient-derived orthotopic xenograft; recurrence; resection; triple-negative breast cancer.