Versari Ilaria, Salucci Sara, Bavelloni Alberto, Battistelli Michela, Traversari Mirko, Wang Ashley, Sampaolesi Maurilio, Faenza Irene
Department of Biomedical and NeuroMotor Sciences (DIBINEM), University of Bologna, 40126 Bologna, Italy.
Laboratory of Experimental Oncology, IRCCS, Istituto Ortopedico Rizzoli, 40136 Bologna, Italy.
Biomolecules. 2025 Feb 25;15(3):334. doi: 10.3390/biom15030334.
Rhabdomyosarcoma (RMS) is a common soft tissue sarcoma primarily affecting children and young adults. This disease is more prevalent in children under 15, with two main types: embryonal Rhabdomyosarcoma (eRMS), which has a better prognosis, and alveolar Rhabdomyosarcoma (aRMS), which is more aggressive and associated with specific genetic alterations. The PI3K-Akt-mTOR pathway is often hyperactivated in RMS, contributing to cell proliferation, survival, and resistance to therapies. The presence of phosphorylated components of this pathway correlates with poor survival outcomes. Here, we discuss various therapeutic approaches targeting the PI3K-Akt-mTOR pathway. These include the use of specific inhibitors (e.g., PI3K inhibitors, Akt inhibitors) and combination therapies that may enhance treatment efficacy. Dietary supplements like curcumin and repurposed drugs such as chloroquine are also mentioned for their potential to induce apoptosis in RMS cells. We also emphasize the need for innovative strategies to improve survival rates, which have remained stagnant over the years. Targeting super-enhancers and transcription factors associated with RMS may provide new therapeutic avenues. Overall, this review underscores the critical role of the PI3K-Akt-mTOR pathway in RMS and the potential for targeted therapies to improve patient outcomes.
横纹肌肉瘤（RMS）是一种常见的软组织肉瘤，主要影响儿童和年轻人。这种疾病在15岁以下儿童中更为普遍，有两种主要类型：预后较好的胚胎性横纹肌肉瘤（eRMS）和侵袭性更强且与特定基因改变相关的肺泡状横纹肌肉瘤（aRMS）。PI3K-Akt-mTOR通路在RMS中常被过度激活，促进细胞增殖、存活及对治疗的抵抗。该通路磷酸化成分的存在与不良生存结果相关。在此，我们讨论针对PI3K-Akt-mTOR通路的各种治疗方法。这些方法包括使用特定抑制剂（如PI3K抑制剂、Akt抑制剂）以及可能提高治疗效果的联合疗法。还提到了姜黄素等膳食补充剂以及氯喹等重新利用的药物诱导RMS细胞凋亡的潜力。我们还强调需要创新策略来提高生存率，多年来生存率一直停滞不前。靶向与RMS相关的超级增强子和转录因子可能提供新的治疗途径。总体而言，本综述强调了PI3K-Akt-mTOR通路在RMS中的关键作用以及靶向治疗改善患者预后的潜力。
