PT - JOURNAL ARTICLE AU - NORIYUKI MASAKI AU - QINGHONG HAN AU - CARISSA SAMONTE AU - NATHANIEL F. WU AU - CHIHIRO HOZUMI AU - JUSTIN WU AU - KOYA OBARA AU - YUTARO KUBOTA AU - YUSUKE AOKI AU - MICHAEL BOUVET AU - ROBERT M. HOFFMAN TI - Oral-recombinant Methioninase in Combination With Rapamycin Eradicates Osteosarcoma of the Breast in a Patient-derived Orthotopic Xenograft Mouse Model AID - 10.21873/anticanres.16028 DP - 2022 Nov 01 TA - Anticancer Research PG - 5217--5222 VI - 42 IP - 11 4099 - http://ar.iiarjournals.org/content/42/11/5217.short 4100 - http://ar.iiarjournals.org/content/42/11/5217.full SO - Anticancer Res2022 Nov 01; 42 AB - Background/Aim: Primary osteosarcoma of the breast is a very rare malignancy that shares histological features with osteosarcoma. It is also highly sensitive to methionine restriction due to methionine addiction. We previously established a patient-derived orthotopic xenograft (PDOX) nude-mouse model derived from tumor tissue of a patient with primary mammary osteosarcoma. In the present study, we investigated the efficacy of oral-recombinant methioninase (o-rMETase), combined with rapamycin, an inhibitor of mammalian target of rapamycin (mTOR) kinase, on a mammary osteosarcoma PDOX nude-mouse model. Materials and Methods: The PDOX mouse model was established by surgically transplanting a specimen of primary osteosarcoma of the breast into the mammary gland of nude mice. Mice implanted with tumors were randomly divided into four groups: Control group, N=5; rapamycin-treated group, N=5; o-rMETase-treated group, N=5; and a group treated with the combination of o-rMETase and rapamycin, N=5. Mice were treated for 2 weeks after transplantation, and tumor volume was measured during the treatment period. Results: Treatment with the combination of rapamycin and o-rMETase eradicated the osteosarcoma of the breast compared to the untreated control (p=0.000008). o-rMETase alone did not significantly inhibit tumor growth, and rapamycin alone only partially inhibited the tumor (p=0.78 and p=0.018, respectively) compared to the untreated control. There was not a significant difference in mouse weight between the groups. Conclusion: The combination of rapamycin and o-rMETase was highly effective against primary osteosarcoma of the breast in a PDOX model, suggesting a future clinical strategy for this rare cancer type that currently has no first-line treatment.