AntiCancer, Inc., San Diego, CA, USA; Department of Surgery, University of California, San Diego, CA, USA; Department of Orthopedic Surgery, Kanazawa University, Kanazawa, Japan.
AntiCancer, Inc., San Diego, CA, USA; Department of Surgery, University of California, San Diego, CA, USA.
Biochem Biophys Res Commun. 2019 May 28;513(2):326-331. doi: 10.1016/j.bbrc.2019.03.191. Epub 2019 Apr 5.
Recurrent osteosarcoma is a chemotherapy-resistant disease. Individualized precision therapy is needed for this disease. Toward this goal, we have developed the patient-derived othotopic xenograft (PDOX) mouse model of all major cancer types including osteosarcoma. Synergistic efficacy of trabectedin (TRAB) and irinotecan (IRT) has been reported in Ewing's sarcoma, soft-tissue sarcoma, and ovarian cancer. However, the efficacy of this combination on osteosarcoma is not known. The goal of present study was to determine the efficacy of the TRAB and IRT combination on cisplatinum (CDDP)-resistant osteosarcoma PDOX. The osteosarcoma PDOX models were randomized into five treatment groups of six mice: Untreated control; CDDP alone; TRAB alone; IRT alone; and TRAB and the IRT combination. Tumor size and body weight were measured during the 14 days of treatment. Tumor growth was regressed only by the TRAB-IRT combination. Tumors treated with the TRAB-IRT combination had the most tumor necrosis with degenerative change. The present study demonstrates the power of the PDOX model to identify a novel effective treatment strategy of the TRAB and IRT combination for chemotherapy-resistant osteosarcoma.
复发性骨肉瘤是一种对化疗有抗性的疾病。这种疾病需要个体化的精准治疗。为此，我们开发了包括骨肉瘤在内的所有主要癌症类型的患者来源的原位异种移植（PDOX）小鼠模型。在尤文肉瘤、软组织肉瘤和卵巢癌中，已经报道了曲贝替定（TRAB）和伊立替康（IRT）的协同疗效。然而，这种联合用药对骨肉瘤的疗效尚不清楚。本研究的目的是确定 TRAB 和 IRT 联合用药对顺铂（CDDP）耐药骨肉瘤 PDOX 的疗效。将骨肉瘤 PDOX 模型随机分为五组，每组 6 只小鼠：未处理对照组；单独使用 CDDP；单独使用 TRAB；单独使用 IRT；以及 TRAB 和 IRT 联合用药。在 14 天的治疗期间测量肿瘤大小和体重。只有 TRAB-IRT 联合用药才能使肿瘤消退。用 TRAB-IRT 联合治疗的肿瘤坏死最多，退行性变化最明显。本研究证明了 PDOX 模型在确定曲贝替定和伊立替康联合治疗化疗耐药骨肉瘤的新有效治疗策略方面的强大作用。
