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Abstract：
Rhabdomyosarcoma (RMS) is a rare soft tissue sarcoma (STS) that predominantly affects children and teenagers. It is the most common STS in children (40%) and accounts for 5-8% of total childhood malignancies. Apart from surgery and radiotherapy in eligible patients, standard chemotherapy is the only therapeutic option clinically available for RMS patients. While survival rates for this childhood cancer have considerably improved over the last few decades for low-risk and intermediate-risk cases, the mortality rate remains exceptionally high in high-risk RMS patients with recurrent and/or metastatic disease. The intensification of chemotherapeutic protocols in advanced-stage RMS has historically induced aggravated toxicity with only very modest therapeutic gain. In this review, we critically analyse what has been achieved so far in RMS therapy and provide insight into how a diverse group of drug-metabolising enzymes (DMEs) possess the capacity to modify the clinical efficacy of chemotherapy. We provide suggestions for new therapeutic strategies that exploit the presence of DMEs for prodrug activation, targeted chemotherapy that does not rely on DMEs, and RMS-molecular-subtype-targeted therapies that have the potential to enter clinical evaluation.
摘要：
横纹肌肉瘤（RMS）是一种罕见的软组织肉瘤（STS），主要影响儿童和青少年。它是儿童中最常见的STS（40％），占儿童恶性肿瘤总数的5-8％。除了对符合条件的患者进行手术和放疗外，标准化疗是临床上可用于RMS患者的唯一治疗选择.虽然在过去的几十年里，这种儿童癌症的生存率在低风险和中等风险病例中得到了相当大的提高，在复发性和/或转移性疾病的高危RMS患者中,死亡率仍然异常高.从历史上看，晚期RMS中化疗方案的强化仅引起非常适度的治疗增益，就引起了加重的毒性。在这次审查中,我们批判性地分析了迄今为止在RMS治疗中取得的成就,并深入了解了一组不同的药物代谢酶(DME)如何具有改变化疗临床疗效的能力.我们为新的治疗策略提供建议，这些策略利用DME的存在进行前药激活，不依赖DME的靶向化疗，和RMS-分子亚型靶向治疗，有可能进入临床评估。
