Ziemba Barbara, Lukow Klaudia
Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, 141/143 Pomorska St., 90-236 Lodz, Poland.
Int J Mol Sci. 2025 May 28;26(11):5204. doi: 10.3390/ijms26115204.
Alveolar rhabdomyosarcoma (ARMS) is a highly aggressive pediatric soft-tissue sarcoma driven by fusion proteins. Despite intensive multimodal therapy, outcomes remain poor for patients with fusion-positive ARMS. This review integrates recent advances in the molecular pathogenesis of ARMS, highlighting key diagnostic and therapeutic targets. We discuss the central role of fusion proteins in transcriptional reprogramming, impaired myogenic differentiation, and super-enhancer activation. Emerging biomarkers (, , P-cadherin) and oncogenic kinases (Aurora A, , PLK1) are evaluated alongside receptor tyrosine kinases (, ) and transcription factors involved in metabolic rewiring (, ). Additionally, we examine immunotherapeutic strategies, epigenetic modifiers, and noncoding RNAs as potential therapeutic avenues. Together, these insights provide a comprehensive framework for developing biomarker-guided, multi-targeted therapies to improve outcomes in ARMS.
肺泡横纹肌肉瘤（ARMS）是一种由融合蛋白驱动的高度侵袭性小儿软组织肉瘤。尽管采用了强化多模式治疗，但融合阳性ARMS患者的预后仍然很差。本综述整合了ARMS分子发病机制的最新进展，突出了关键的诊断和治疗靶点。我们讨论了融合蛋白在转录重编程、肌源性分化受损和超级增强子激活中的核心作用。同时评估了新兴生物标志物（、、P-钙黏蛋白）和致癌激酶（极光激酶A、、PLK1）以及参与代谢重塑的受体酪氨酸激酶（、）和转录因子。此外，我们还研究了免疫治疗策略、表观遗传修饰剂和非编码RNA作为潜在的治疗途径。这些见解共同为开发生物标志物引导的多靶点疗法以改善ARMS的预后提供了一个全面的框架。
