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

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

Research output: Contribution to journalArticlepeer-review

45 Citations (Scopus)

Abstract

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 mm3;: 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 mm3; ; CDDP (G2): 608.6±126.9 mm3; \; TRAB (G3): 286.6±133.0 mm3; TEM (G4): 182.9±69.1 mm3; . 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.

Original languageEnglish
Pages (from-to)62111-62119
Number of pages9
JournalOncotarget
Volume8
Issue number37
DOIs
Publication statusPublished - 2017 Sep 1
Externally publishedYes

Keywords

  • Chemotherapy
  • Lung metastasis
  • Osteosarcoma
  • PDOX
  • Recurrence

ASJC Scopus subject areas

  • Oncology

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