Inoue Masahiro, Horiuchi Keisuke, Susa Michiro, Taguchi Eiko, Ishizaka Takahiro, Rikitake Hajime, Matsuhashi Yusuke, Chiba Kazuhiro
Department of Orthopedic Surgery, National Defense Medical College, Tokorozawa, Saitama, Japan.
Department of Orthopedic Surgery, Keio University School of Medicine, Tokyo, Japan.
J Orthop Res. 2022 Apr;40(4):945-953. doi: 10.1002/jor.25105. Epub 2021 Jun 9.
Osteosarcoma (OS) is the most common primary bone tumor that mainly affects adolescents and young adults. Although standard treatment modality can achieve up to 60%-70% 5-year survival rate, there has not been any substantial improvement over the past four decades. Furthermore, those presenting with pulmonary metastatic lesions often undergo a highly unfavorable clinical course. Therefore, there is a severely unmet clinical need to provide a more effective treatment for patients with OS. In this study, we show that trabectedin (TBD), a chemotherapeutic agent approved for soft tissue sarcomas, significantly suppresses pulmonary metastasis in a mouse OS xenograft model. In vitro experiments revealed that TBD suppresses cell migration potentially by downregulating the activity of ERK1/2, intracellular molecules that are critically involved in the regulation of cell motility. Collectively, our data may provide a basis for further investigation of TBD on the potential use for OS patients who are at great risk of pulmonary metastasis.
骨肉瘤（OS）是最常见的原发性骨肿瘤，主要影响青少年和青年。尽管标准治疗方式可使5年生存率达到60%-70%，但在过去四十年中并未有任何实质性改善。此外，那些出现肺转移病变的患者通常会经历非常不利的临床病程。因此，为骨肉瘤患者提供更有效治疗存在严重未满足的临床需求。在本研究中，我们表明曲贝替定（TBD），一种已被批准用于软组织肉瘤的化疗药物，在小鼠骨肉瘤异种移植模型中显著抑制肺转移。体外实验表明，TBD可能通过下调ERK1/2的活性来抑制细胞迁移，ERK1/2是细胞内关键参与细胞运动调节的分子。总体而言，我们的数据可能为进一步研究TBD在有高肺转移风险的骨肉瘤患者中的潜在应用提供基础。
