Department of Clinical Medicine, Thoracic Oncology Research Group, Trinity College Dublin, St. James's Hospital Ireland Dublin, Ireland.
Front Oncol. 2013 May 16;3:120. doi: 10.3389/fonc.2013.00120. eCollection 2013.
Intrinsic or acquired resistance to chemotherapeutic agents is a common phenomenon and a major challenge in the treatment of cancer patients. Chemoresistance is defined by a complex network of factors including multi-drug resistance proteins, reduced cellular uptake of the drug, enhanced DNA repair, intracellular drug inactivation, and evasion of apoptosis. Pre-clinical models have demonstrated that many chemotherapy drugs, such as platinum-based agents, antracyclines, and taxanes, promote the activation of the NF-κB pathway. NF-κB is a key transcription factor, playing a role in the development and progression of cancer and chemoresistance through the activation of a multitude of mediators including anti-apoptotic genes. Consequently, NF-κB has emerged as a promising anti-cancer target. Here, we describe the role of NF-κB in cancer and in the development of resistance, particularly cisplatin. Additionally, the potential benefits and disadvantages of targeting NF-κB signaling by pharmacological intervention will be addressed.
内在或获得性对化疗药物的耐药性是一种常见现象，也是癌症患者治疗的主要挑战。耐药性是由多种因素构成的复杂网络定义的，包括多药耐药蛋白、细胞内药物摄取减少、增强的 DNA 修复、细胞内药物失活以及逃避细胞凋亡。临床前模型表明，许多化疗药物，如铂类药物、蒽环类药物和紫杉烷类药物，可促进 NF-κB 通路的激活。NF-κB 是一种关键的转录因子，通过激活多种介质，包括抗凋亡基因，在癌症的发生和进展以及耐药性中发挥作用。因此，NF-κB 已成为有前途的抗癌靶点。在这里，我们描述了 NF-κB 在癌症和耐药性发展中的作用，特别是顺铂。此外，还将讨论通过药理干预靶向 NF-κB 信号的潜在益处和弊端。
