Dysregulated transcription factors (TFs) fuel aberrant gene expression networks, resulting in cell overproliferation, migration, and immunosuppression. Given that TFs are regarded to have vital roles in tumors, various approaches are exploited to modulate their activities. Nevertheless, except for some ligand-binding nuclear receptors, most TFs are still considered ‘undruggable’ targets. Responding to extra- or intracellular stimuli, TFs are decorated with an array of post-translational modifications (PTMs) to regulate their subcellular localizations, protein–protein/DNA interactions, and stability. These PTMs orchestrate the multiple functions of TFs, thus offering numerous potential targets. In this review, we systematically review emerging concepts and effective agents in PTMs-associated TF-targeting, which could provide paradigms for cancer treatment.

失调的转录因子 (TF) 为异常的基因表达网络提供燃料，导致细胞过度增殖、迁移和免疫抑制。鉴于 TFs 被认为在肿瘤中具有重要作用，因此利用各种方法来调节它们的活动。尽管如此，除了一些配体结合核受体，大多数 TF 仍然被认为是“不可成药”的目标。响应细胞外或细胞内刺激，TF 被一系列翻译后修饰 (PTM) 修饰，以调节其亚细胞定位、蛋白质-蛋白质/DNA 相互作用和稳定性。这些 PTM 协调了 TF 的多种功能，从而提供了许多潜在的目标。在这篇综述中，我们系统地回顾了 PTM 相关 TF 靶向中的新兴概念和有效代理，