奥拉单抗联合多柔比星和异环磷酰胺克服了未分化软组织肉瘤在 PDOX 小鼠模型中对多柔比星和奥拉单抗的个体耐药性。
Olaratumab combined with doxorubicin and ifosfamide overcomes individual doxorubicin and olaratumab resistance of an undifferentiated soft-tissue sarcoma in a PDOX mouse model.
机构信息
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.
出版信息
Cancer Lett. 2019 Jun 1;451:122-127. doi: 10.1016/j.canlet.2019.03.003. Epub 2019 Mar 10.
Olaratumab (OLA), a monoclonal antibody against platelet-derived growth factor receptor alpha (PDGFRα), has recently been used against soft-tissue sarcoma (STS) combined with doxorubicin (DOX), with limited efficacy. The goal of the present study was to determine the efficacy of OLA in combination with DOX and ifosfamide (IFO) on STS. Undifferentiated soft-tissue sarcoma (USTS) from a striated muscle of a patient was grown orthotopically in the right biceps femoris muscle of nude mice to establish USTS patient-derived orthotopic xenograft (PDOX) model. USTS PDOX tumors were treated with OLA alone, DOX alone, DOX combined with IFO, OLA combined with DOX or IFO, and OLA combined with DOX and IFO. Tumor size and body weight were measured during the 14 days of treatment. Tumor growth was arrested by OLA combined with DOX and IFO. Tumors treated with OLA combined with DOX and IFO had the most necrosis. The present study demonstrates the power of the PDOX model to identify the novel effective treatment strategy of the combination of OLA, DOX and IFO for soft-tissue sarcomas.
奥拉单抗（OLA）是一种针对血小板衍生生长因子受体α（PDGFRα）的单克隆抗体，最近已被用于联合多柔比星（DOX）治疗软组织肉瘤（STS），但疗效有限。本研究旨在确定 OLA 联合 DOX 和异环磷酰胺（IFO）治疗 STS 的疗效。将患者横纹肌肉来源的未分化软组织肉瘤（USTS）在裸鼠右股二头肌中进行原位种植，建立 USTS 患者来源的原位异种移植（PDOX）模型。用 OLA 单药、DOX 单药、DOX 联合 IFO、OLA 联合 DOX 或 IFO、以及 OLA 联合 DOX 和 IFO 对 USTS PDOX 肿瘤进行治疗。在 14 天的治疗期间测量肿瘤大小和体重。OLA 联合 DOX 和 IFO 可抑制肿瘤生长。OLA 联合 DOX 和 IFO 治疗的肿瘤坏死最多。本研究证明了 PDOX 模型在确定 OLA、DOX 和 IFO 联合治疗软组织肉瘤的新型有效治疗策略方面的强大作用。
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