Targeted therapies have revolutionized cancer treatment; however, progress lags behind in alveolar (ARMS) and embryonal rhabdomyosarcoma (ERMS), a soft-tissue sarcoma mainly occurring at pediatric and young adult age. Insulin-like growth factor 1 receptor (IGF1R)-directed targeted therapy is one of the few single-agent treatments with clinical activity in these diseases. However, clinical effects only occur in a small subset of patients and are often of short duration due to treatment resistance. Rational selection of combination treatments of either multiple targeted therapies or targeted therapies with chemotherapy could hypothetically circumvent treatment resistance mechanisms and enhance clinical efficacy. Simultaneous targeting of distinct mechanisms might be of particular interest in this regard, as this affects multiple hallmarks of cancer at once. To determine the most promising and clinically relevant targeted therapy–based combination treatments for ARMS and ERMS, we provide an extensive overview of preclinical and (early) clinical data concerning a variety of targeted therapy–based combination treatments. We concentrated on the most common classes of targeted therapies investigated in rhabdomyosarcoma to date, including those directed against receptor tyrosine kinases and associated downstream signaling pathways, the Hedgehog signaling pathway, apoptosis pathway, DNA damage response, cell-cycle regulators, oncogenic fusion proteins, and epigenetic modifiers. Mol Cancer Ther; 17(7); 1365–80. ©2018 AACR.

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基于靶向治疗的横纹肌肉瘤联合治疗

靶向治疗彻底改变了癌症治疗；然而，肺泡 (ARMS) 和胚胎横纹肌肉瘤 (ERMS) 的进展滞后，这是一种主要发生在儿童和青年时期的软组织肉瘤。胰岛素样生长因子 1 受体 (IGF1R) 导向的靶向治疗是为数不多的对这些疾病具有临床活性的单药治疗之一。然而，临床效果仅发生在一小部分患者中，并且由于治疗抵抗而通常持续时间很短。合理选择多种靶向治疗或靶向治疗与化疗的联合治疗可以假设规避治疗耐药机制并提高临床疗效。在这方面，同时针对不同机制可能特别感兴趣，因为这会同时影响癌症的多个标志。为了确定最有希望和临床相关的基于靶向治疗的 ARMS 和 ERMS 联合治疗，我们提供了有关各种基于靶向治疗的联合治疗的临床前和（早期）临床数据的广泛概述。我们专注于迄今为止在横纹肌肉瘤中研究的最常见的靶向疗法类别，包括针对受体酪氨酸激酶和相关下游信号通路、Hedgehog 信号通路、细胞凋亡通路、DNA 损伤反应、细胞周期调节剂、致癌融合蛋白、和表观遗传修饰符。摩尔癌症治疗; 17(7); 1365-80。©2018 AACR。我们提供了有关各种基于靶向治疗的联合治疗的临床前和（早期）临床数据的广泛概述。我们专注于迄今为止在横纹肌肉瘤中研究的最常见的靶向疗法类别，包括针对受体酪氨酸激酶和相关下游信号通路、Hedgehog 信号通路、细胞凋亡通路、DNA 损伤反应、细胞周期调节剂、致癌融合蛋白、和表观遗传修饰符。摩尔癌症治疗; 17(7); 1365-80。©2018 AACR。我们提供了有关各种基于靶向治疗的联合治疗的临床前和（早期）临床数据的广泛概述。我们专注于迄今为止在横纹肌肉瘤中研究的最常见的靶向疗法类别，包括针对受体酪氨酸激酶和相关下游信号通路、Hedgehog 信号通路、细胞凋亡通路、DNA 损伤反应、细胞周期调节剂、致癌融合蛋白、和表观遗传修饰符。摩尔癌症治疗; 17(7); 1365-80。©2018 AACR。包括针对受体酪氨酸激酶和相关下游信号通路、刺猬信号通路、细胞凋亡通路、DNA 损伤反应、细胞周期调节剂、致癌融合蛋白和表观遗传修饰剂的那些。摩尔癌症治疗; 17(7); 1365-80。©2018 AACR。包括针对受体酪氨酸激酶和相关下游信号通路、刺猬信号通路、细胞凋亡通路、DNA 损伤反应、细胞周期调节剂、致癌融合蛋白和表观遗传修饰剂的那些。摩尔癌症治疗; 17(7); 1365-80。©2018 AACR。