Picher Enric Arasanz, Wahajuddin Muhammad, Barth Stefan, Chisholm Julia, Shipley Janet, Pors Klaus
Institute of Cancer Therapeutics, Faculty of Life Sciences, University of Bradford, Bradford BD7 1DP, UK.
Medical Biotechnology and Immunotherapy Research Unit, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town 7700, South Africa.
Cancers (Basel). 2024 Feb 29;16(5):1012. doi: 10.3390/cancers16051012.
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。虽然在过去几十年中，低风险和中风险的儿童癌症患者的生存率有了显著提高，但高风险的复发性和/或转移性RMS患者的死亡率仍然异常高。在晚期RMS中强化化疗方案历来会导致毒性加剧，而治疗收益却非常有限。在本综述中，我们批判性地分析了RMS治疗目前所取得的成果，并深入探讨了多种药物代谢酶（DME）如何能够改变化疗的临床疗效。我们为新的治疗策略提供建议，这些策略包括利用DME进行前药激活、不依赖DME的靶向化疗以及有可能进入临床评估的RMS分子亚型靶向治疗。
