Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117593, Singapore.
Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117593, Singapore.
Redox Biol. 2019 Jul;25:101124. doi: 10.1016/j.redox.2019.101124. Epub 2019 Jan 25.
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不良。抗 RMS 治疗包括手术、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，它们已经趋于稳定。此外，目前的治疗方法具有侵袭性，耐药性和转移导致几种治疗方案失败。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，并为治疗开辟了新途径。在高通量药物筛选研究中确定的一个重要靶点是活性氧物种 (ROS)。事实上，RMS 临床试验中的许多药物都通过 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 RMS 中 ROS 的影响，这些为开发 RMS 的新型分子靶向治疗奠定了基础。这种靶向治疗与传统治疗相结合，可以减少年轻幸存者的不良反应，并降低长期发病率。
