Childhood cancer is rare, with about 1 in 260 children developing cancer before age 20. However, it remains a leading cause of death for children and adolescents worldwide. The 5-year survival rate for childhood cancer in high-income countries exceeds 80%, but globally, the average survival rate is around 37%, highlighting significant disparities across the globe. Despite the life-saving impact of current treatment regimens, long-term side effects and risks are always concerns. Therefore, there is a continuing urgent need for novel therapies to overcome the limitations of existing approaches and improve patient outcomes. Targeted drug therapies that interfere with cancer-causing genes play a vital role in cancer treatment by specifically targeting cancer cells. TFs are primary drivers of gene expression that are critical in various pediatric cancers. Chromosomal rearrangements, involving changes in chromosome structure such as deletions, duplications, inversions, and translocations, can significantly alter TF activity and downstream gene expression. Dysregulation of TFs disrupts gene expression networks and has been strongly linked to the development and progression of many pediatric cancers, making them promising therapeutic targets. Several approaches targeting TFs, including small-molecule inhibitors designed to block TF-DNA binding, TF-cofactor interactions, or their epigenetic regulation, as well as RNA interference, have been developed. More recently, approaches like PROTACs (Proteolysis-Targeting Chimeras) and molecular glue degraders offer new therapeutic possibilities in pediatric cancers. These innovations represent a paradigm shift in pediatric oncology, offering hope for more targeted, less toxic treatment options. This review discusses the critical role of TFs in childhood cancers and emphasizes the need for evolving therapeutic strategies aimed at targeting these key regulators to improve outcomes for young patients.
儿童癌症较为罕见，约每260名儿童中会有1名在20岁前罹患癌症。然而，该疾病仍是全球儿童和青少年的主要死因之一。在高收入国家，儿童癌症的五年生存率超过80%，但全球平均生存率仅为37%左右，凸显了不同地区间的显著差异。尽管现有治疗方案具有挽救生命的效果，但长期副作用和风险始终备受关注。因此，亟需开发新型疗法以突破现有治疗手段的局限，改善患者预后。针对致癌基因的靶向药物疗法通过特异性作用于癌细胞，在癌症治疗中发挥着关键作用。转录因子作为基因表达的主要驱动因子，在多种儿童癌症中至关重要。染色体结构变异（如缺失、重复、倒位和易位）可显著改变转录因子活性及其下游基因表达。转录因子失调会破坏基因表达网络，并与多种儿童癌症的发生发展密切相关，这使其成为极具潜力的治疗靶点。目前已有多种靶向转录因子的策略被开发出来，包括旨在阻断转录因子与DNA结合、干扰转录因子与辅因子相互作用或调控其表观遗传修饰的小分子抑制剂，以及RNA干扰技术。近年来，蛋白水解靶向嵌合体和分子胶降解剂等新策略为儿童癌症治疗提供了新的可能性。这些创新代表了儿童肿瘤学领域的范式转变，为开发更具靶向性、毒性更低的治疗方案带来了希望。本综述探讨了转录因子在儿童癌症中的关键作用，并强调需要不断发展针对这些关键调控因子的治疗策略，以改善年轻患者的预后。
Masters of Gene Expression: Transcription Factors in Pediatric Cancers
肿瘤(癌症)患者之家