Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma accounting for 5–8% of malignant tumours in children and adolescents. Children with high risk disease have poor prognosis. Anti-RMS therapies include surgery, radiation and combination chemotherapy. While these strategies improved survival rates, they have plateaued since 1990s as drugs that target differentiation and self-renewal of tumours cells have not been identified. Moreover, prevailing treatments are aggressive with drug resistance and metastasis causing failure of several treatment regimes. Significant advances have been made recently in understanding the genetic and epigenetic landscape in RMS. These studies have identified novel diagnostic and prognostic markers and opened new avenues for treatment. An important target identified in high throughput drug screening studies is reactive oxygen species (ROS). Indeed, many drugs in clinical trials for RMS impact tumour progression through ROS. In light of such emerging evidence, we discuss recent findings highlighting key pathways, epigenetic alterations and their impacts on ROS that form the basis of developing novel molecularly targeted therapies in RMS. Such targeted therapies in combination with conventional therapy could reduce adverse side effects in young survivors and lead to a decline in long-term morbidity.

横纹肌肉瘤（RMS）是最常见的软组织肉瘤，占儿童和青少年恶性肿瘤的5%~8%。患有高危疾病的儿童预后较差。抗 RMS 疗法包括手术、放疗和联合化疗。虽然这些策略提高了生存率，但自 20 世纪 90 年代以来，由于尚未确定针对肿瘤细胞分化和自我更新的药物，它们已趋于稳定。此外，流行的治疗具有侵略性，具有耐药性和转移性，导致多种治疗方案失败。最近在理解 RMS 的遗传和表观遗传景观方面取得了重大进展。这些研究确定了新的诊断和预后标志物，并开辟了新的治疗途径。高通量药物筛选研究中确定的一个重要目标是活性氧（ROS）。事实上，许多 RMS 临床试验中的药物通过 ROS 影响肿瘤进展。鉴于这些新出现的证据，我们讨论了最近的发现，强调了关键途径、表观遗传改变及其对 ROS 的影响，这些影响构成了开发 RMS 新型分子靶向疗法的基础。这种靶向治疗与常规治疗相结合可以减少年轻幸存者的不良副作用，并导致长期发病率下降。