A patient-derived orthotopic xenograft (PDOX) mouse model of a cisplatinum-resistant osteosarcoma lung metastasis that was sensitive to temozolomide and trabectedin: implications for precision oncology

作者：Igarashi Kentaro; Murakami Takashi; Kawaguchi Kei; Kiyuna Tasuku; Miyake Kentaro; Zhang Yong; Nelson Scott D; Dry Sarah M; Li Yunfeng; Yanagawa Jane; Russell Tara A; Singh Arun S; Tsuchiya Hiroyuki; Elliott Irmina; Eilber Fritz C^*; Hoffman Robert M^*

来源：Oncotarget, 2017, 8(37): 62111-62119.

DOI：10.18632/oncotarget.19095

• osteosarcoma
• recurrence
• lung metastasis
• PDOX
• chemotherapy

In the present study, we evaluated the efficacy of trabectedin (TRAB) and temozolomide (TEM) compared to cisplatinum (CDDP) on a patient-derived orthotopic xenogrraft (PDOX) of a lung-metastasis from an osteosarcoma of a patient who failed CDDP therapy. Osteosarcoma resected from the patient was implanted orthotopically in the distal femur of mice to establish PDOX models which were randomized into the following groups when tumor volume reached approximately 100 mm(3): G1, control without treatment; G2, CDDP (6 mg/kg, intraperitoneal injection, weekly, for 2 weeks); G3, TRAB (0.15 mg/kg, intravenous injection, weekly, for 2 weeks); G4, TEM (25 mg/kg, oral, daily, for 14 days). Tumor size and body weight were measured with calipers and a digital balance, respectively, twice a week. On day 14 after initiation of treatment, TEM and TRAB, but not CDDP, significantly inhibited tumor volume compared to untreated control: control (G1): 814.5 +/- 258.8 mm(3); CDDP (G2): 608.6 +/- 126.9 mm(3); TRAB (G3): 286.6 +/- 133.0 mm(3); TEM (G4): 182.9 +/- 69.1 mm(3). CDDP vs. control, p=0.07; TRAB vs. control, p=0.0004; TEM vs. control p=0.0002; TRAB vs. CDDP, p=0.0002; TEM vs. CDDP, p=0.00003. The results of the present study show that a PDOX model of an osteosarcoma lung-metastasis that recurred after adjuvant CDDP-treatment has identified potentially, highly-effective drugs for this recalcitrant disease, while accurately maintaining the CDDP resistance of the tumor in the patient, thereby demonstrating the potential of the osteosarcoma PDOX model for precision oncology.

• 出版日期2017-9-5