Precision (individualized) medicine relies on the molecular profiling of tumors’ dysregulated characteristics (genomic, epigenetic, transcriptomic) to identify the reliance on key pathways (including genome stability and epigenetic gene regulation) for viability or growth, and then utilises targeted therapeutics to disrupt these survival-dependent pathways. Non-mutational epigenetic changes alter cells’ transcriptional profile and are a key feature found in many tumors. In contrast to genetic mutations, epigenetic changes are reversable, and restoring a normal epigenetic profile can inhibit tumor growth and progression. Lysine acetyltransferases (KATs or HATs) protect genome stability and integrity, and Tip60 is an essential acetyltransferase due to its roles as an epigenetic and transcriptional regulator, and as master regulator of the DNA double-strand break response. Tip60 is commonly downregulated and mislocalized in many cancers, and the roles that mislocalized Tip60 plays in cancer are not well understood. Here we categorize and discuss Tip60-regulated genes, evaluate Tip60-interacting proteins based on cellular localization, and explore the therapeutic potential of Tip60-targeting compounds as epigenetic inhibitors. Understanding the multiple roles Tip60 plays in tumorigenesis will improve our understanding of tumor progression and will inform therapeutic options, including informing potential combinatorial regimes with current chemotherapeutics, leading to improvements in patient outcomes.
精准（个体化）医疗依赖于对肿瘤失调特征（基因组、表观遗传、转录组）的分子谱分析，以识别肿瘤生存或生长所依赖的关键通路（包括基因组稳定性与表观遗传基因调控），进而利用靶向治疗手段破坏这些生存依赖性通路。非突变性表观遗传改变会调控细胞的转录谱，是多种肿瘤的关键特征。与基因突变不同，表观遗传改变具有可逆性，恢复正常的表观遗传谱可抑制肿瘤生长与进展。赖氨酸乙酰转移酶（KATs或HATs）对维持基因组稳定性与完整性具有保护作用，其中Tip60作为关键乙酰转移酶，兼具表观遗传调控、转录调控及DNA双链断裂应答主调控因子等多重功能。Tip60在多种癌症中普遍存在表达下调与定位异常的现象，但其异常定位在癌症中的作用机制尚未明确。本文系统归类并探讨了Tip60调控的基因，基于细胞定位评估了Tip60相互作用蛋白，并探索了靶向Tip60化合物作为表观遗传抑制剂的治疗潜力。深入理解Tip60在肿瘤发生中的多重作用，将增进我们对肿瘤进展的认知，并为治疗策略（包括与现有化疗药物的潜在联合方案）提供理论依据，最终改善患者预后。
肿瘤(癌症)患者之家