Sahlgrenska Cancer Center, Department of Pathology, University of Gothenburg, 405 30 Gothenburg, Sweden.
Cells. 2019 Aug 16;8(8):913. doi: 10.3390/cells8080913.
Chromosome rearrangements resulting in pathogenetically important gene fusions are a common feature of many cancers. They are often potent oncogenic drivers and have key functions in central cellular processes and pathways and encode transcription factors, transcriptional co-regulators, growth factor receptors, tyrosine kinases, and chromatin modifiers. In addition to being useful diagnostic biomarkers, they are also targets for development of new molecularly targeted therapies. Studies in recent decades have shown that several oncogenic gene fusions interact with the insulin-like growth factor (IGF) signaling pathway. For example, the MYB-NFIB fusion in adenoid cystic carcinoma is regulated by IGF1R through an autocrine loop, and IGF1R is a downstream target of the EWSR1-WT1 and PAX3-FKHR fusions in desmoplastic small round cell tumors and alveolar rhabdomyosarcoma, respectively. Here, we will discuss the mechanisms behind the interactions between oncogenic gene fusions and the IGF signaling pathway. We will also discuss the role of therapeutic inhibition of IGF1R in fusion gene driven malignancies.
导致具有重要病理意义的基因融合的染色体重排是许多癌症的一个共同特征。它们通常是强有力的致癌驱动因子，在细胞的核心过程和途径中具有关键功能，并编码转录因子、转录共调节因子、生长因子受体、酪氨酸激酶和染色质修饰因子。除了作为有用的诊断生物标志物外，它们也是开发新的分子靶向治疗方法的靶点。近几十年来的研究表明，几种致癌基因融合与胰岛素样生长因子 (IGF) 信号通路相互作用。例如，腺样囊性癌中的 MYB-NFIB 融合通过自分泌环受 IGF1R 调控，IGF1R 是 EWSR1-WT1 和 PAX3-FKHR 融合在促结缔组织增生性小圆细胞肿瘤和肺泡横纹肌肉瘤中的下游靶点。在这里，我们将讨论致癌基因融合与 IGF 信号通路相互作用的背后机制。我们还将讨论 IGF1R 治疗性抑制在融合基因驱动的恶性肿瘤中的作用。
