University Children's Hospital, Children's Research Center and Department of Oncology, Steinwiesstrasse 75, CH-8032 Zürich, Switzerland.
University Children's Hospital, Children's Research Center and Department of Oncology, Steinwiesstrasse 75, CH-8032 Zürich, Switzerland.
Semin Cancer Biol. 2018 Jun;50:115-123. doi: 10.1016/j.semcancer.2017.11.006. Epub 2017 Nov 14.
Driver oncogenes are prime targets for therapy in tumors many of which, including leukemias and sarcomas, express recurrent fusion transcription factors. One specific example for such a cancer type is alveolar rhabdomyosarcoma, which is associated in the majority of cases with the fusion protein PAX3-FOXO1. Since fusion transcription factors are challenging targets for development of small molecule inhibitors, indirect inhibitory strategies for this type of oncogenes represent a more promising approach. One can envision strategies at different molecular levels including upstream modifiers and activators, epigenetic and transcriptional co-regulators, and downstream effector targets. In this review, we will discuss the current knowledge regarding potential therapeutic targets that might contribute to indirect interference with PAX3-FOXO1 activity in alveolar rhabdomyosarcoma at the different molecular levels and extrapolate these findings to fusion transcription factors in general.
驱动癌基因是许多肿瘤治疗的主要靶点，包括白血病和肉瘤，它们表达反复出现的融合转录因子。这种癌症类型的一个具体例子是肺泡横纹肌肉瘤，大多数情况下与融合蛋白 PAX3-FOXO1 相关。由于融合转录因子是小分子抑制剂开发的挑战性靶点，因此针对这种癌基因的间接抑制策略代表了一种更有前途的方法。人们可以在不同的分子水平上设想策略，包括上游调节剂和激活剂、表观遗传和转录共调节剂以及下游效应靶标。在这篇综述中，我们将讨论当前关于潜在治疗靶点的知识，这些靶点可能有助于在不同的分子水平上间接干扰肺泡横纹肌肉瘤中 PAX3-FOXO1 的活性，并将这些发现推断到一般的融合转录因子。
