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.
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（占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RMS患者唯一可用的治疗选择。尽管在过去几十年中，低危和中危病例的生存率显著提高，但对于复发和/或转移性疾病的高危RMS患者，死亡率仍然异常高。在晚期RMS中强化化疗方案历来会加剧毒性，而治疗效果却非常有限。在本综述中，我们批判性地分析了迄今为止在RMS治疗中取得的成就，并深入探讨了多种药物代谢酶（DMEs）如何具备改变化疗临床疗效的能力。我们提出了新的治疗策略建议，包括利用DMEs进行前药活化、不依赖DMEs的靶向化疗，以及有望进入临床评估的RMS分子亚型靶向疗法。
肿瘤(癌症)患者之家