Vazquez-Santillan K, Melendez-Zajgla J, Jimenez-Hernandez L, Martínez-Ruiz G, Maldonado V
Epigenetics Laboratory, National Institute of Genomic Medicine, Periferico Sur 4809, Arenal Tepepan, Tlalpan, Mexico City, 14610, Mexico.
Functional Cancer Genomics laboratory, National Institute of Genomic Medicine, Periferico Sur 4809, Arenal Tepepan, Tlalpan, Mexico, Mexico City, 14610, Mexico.
Cell Oncol (Dordr). 2015 Oct;38(5):327-39. doi: 10.1007/s13402-015-0236-6. Epub 2015 Aug 29.
Cancer stem cells (CSCs) are regulated by several signaling pathways that ultimately control their maintenance and expansion. NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) forms a protein complex that controls DNA transcription and, as such, plays an important role in proliferation, inflammation, angiogenesis, invasion and metastasis. The NF-κB signaling pathway, which has been found to be constitutively activated in CSCs from a variety of cancers, participates in the maintenance, expansion, proliferation and survival of CSCs. Targeted disruption of this pathway may profoundly impair the adverse phenotype of CSCs and may provide a therapeutic opportunity to remove the CSC fraction. In particular, it may be attractive to use specific NF-κB inhibitors in chronic therapeutic schemes to reduce disease progression. Exceptional low toxicity profiles of these inhibitors are a prerequisite for use in combined treatment regimens and to avoid resistance.
Although still preliminary, recent evidence shows that such targeted strategies may be useful in adjuvant chemo-preventive settings.
癌症干细胞（CSCs）受多种信号通路调控，这些信号通路最终控制其维持和扩增。核因子κB（NF-κB，即活化B细胞核因子κ轻链增强子）形成一种控制DNA转录的蛋白质复合物，因此在增殖、炎症、血管生成、侵袭和转移中发挥重要作用。已发现NF-κB信号通路在多种癌症的CSCs中持续激活，参与CSCs的维持、扩增、增殖和存活。对该信号通路进行靶向破坏可能会严重损害CSCs的不良表型，并可能提供一个清除CSC组分的治疗机会。特别是，在慢性治疗方案中使用特异性NF-κB抑制剂以减少疾病进展可能具有吸引力。这些抑制剂极低的毒性特征是用于联合治疗方案并避免耐药性的先决条件。
尽管仍处于初步阶段，但最近的证据表明，这种靶向策略可能在辅助化学预防环境中有用。
