Gene fusions with translocations involving nuclear receptor coactivators (NCoAs) are relatively common among fusion-driven malignancies. NCoAs are essential mediators of environmental cues and can modulate the transcription of downstream target genes upon binding to activated nuclear receptors. Therefore, fusion proteins containing NCoAs can become strong oncogenic drivers, affecting the cell transcriptional profile. These tumors show a strong dependency on the fusion oncogene; therefore, the direct pharmacological targeting of the fusion protein becomes an attractive strategy for therapy. Currently, different combinations of chemotherapy regimens are used to treat a variety of NCoA-fusion-driven tumors, but given the frequent tumor reoccurrence, more efficient treatment strategies are needed. Specific approaches directed towards inhibition or silencing of the fusion gene need to be developed while minimizing the interference with the original genes. This review highlights the relevant literature describing the normal function and structure of NCoAs and their oncogenic activity in NCoA-gene fusion-driven cancers, and explores potential strategies that could be effective in targeting these fusions.

中文翻译：

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p160 核受体共激活因子家族成员及其在罕见融合驱动肿瘤中的作用（综述）。

涉及核受体共激活子（NCoA）的基因融合和易位在融合驱动的恶性肿瘤中相对常见。 NCoA 是环境信号的重要介质，可以在与激活的核受体结合后调节下游靶基因的转录。因此，含有 NCoA 的融合蛋白可以成为强致癌驱动因素，影响细胞转录谱。这些肿瘤表现出对融合癌基因的强烈依赖性；因此，融合蛋白的直接药理学靶向成为一种有吸引力的治疗策略。目前，不同的化疗方案组合被用于治疗多种NCoA融合驱动的肿瘤，但鉴于肿瘤频繁复发，需要更有效的治疗策略。需要开发针对融合基因的抑制或沉默的具体方法，同时尽量减少对原始基因的干扰。本综述重点介绍了描述 NCoA 的正常功能和结构及其在 NCoA 基因融合驱动的癌症中的致癌活性的相关文献，并探讨了可有效靶向这些融合的潜在策略。