Molecular Pathways: The Balance between Cancer and the Immune System Challenges the Therapeutic Specificity of Targeting Nuclear Factor-κB Signaling for Cancer Treatment.
Molecular Pathways: The Balance between Cancer and the Immune System Challenges the Therapeutic Specificity of Targeting Nuclear Factor-κB Signaling for Cancer Treatment.
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DOI：
10.1158/1078-0432.ccr-15-1374
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发表时间：
2016-09-01
期刊：
影响因子：
--
通讯作者：
Annunziata CM
中科院分区：
文献类型：
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作者：
Zeligs KP;Neuman MK;Annunziata CM
核因子-κB（NF-κB）信号通路是一个连接细胞外刺激与细胞存活和增殖的复杂网络。激活NF-κ B的细胞质信号传导可以作为DNA损伤反应的一部分或响应于包括病毒、炎症和细胞死亡在内的多种激活剂而发生。NF-κB转录因子在肿瘤发生中起重要作用，并与血液肿瘤和实体瘤类型（包括黑色素瘤、乳腺癌、前列腺癌、卵巢癌、胰腺癌、结肠癌、肺癌和甲状腺癌）的起源和传播有关。另一方面，NF-kB信号传导是免疫功能的关键，并且可能是抗肿瘤免疫所必需的。这在设计靶向NF-kB的治疗方法时呈现出困境。人们对鉴定抑制NF-κB活性的新型调节剂越来越感兴趣，因为阻碍NF-κB途径的不同步骤具有减缓肿瘤生长、进展和对化疗的抗性的潜力。尽管我们对这一途径的理解取得了重大进展，但由于正常组织中的靶向效应，我们在临床上有效阻断癌症治疗关键靶点的能力仍然有限。肿瘤特异性对于开发靶向这种抗凋亡信号传导途径的治疗策略至关重要，以便在将这种疗法应用于患者时维持抗肿瘤免疫监视。
The Nuclear Factor-κB (NF-κB) signaling pathway is a complex network linking extracellular stimuli to cell survival and proliferation. Cytoplasmic signaling to activate NF-kB can occur as part of the DNA damage response or in response to a large variety of activators including viruses, inflammation, and cell death. NF-κB transcription factors play a fundamental role in tumorigenesis and are implicated in the origination and propagation of both hematologic and solid tumor types, including melanoma, breast, prostate, ovarian, pancreatic, colon, lung, and thyroid cancers. On the other hand, NF-kB signaling is key to immune function, and is likely necessary for anti-tumor immunity. This presents a dilemma when designing therapeutic approaches to target NF-kB. There is growing interest in identifying novel modulators to inhibit NF-κB activity since impeding different steps of the NF-κB pathway has potential to slow tumor growth, progression, and resistance to chemotherapy. Despite significant advances in our understanding of this pathway, our ability to effectively clinically block key targets for cancer therapy remains limited due to on-target effects in normal tissues. Tumor specificity is critical to developing therapeutic strategies targeting this anti-apoptotic signaling pathway in order to maintain anti-tumor immune surveillance when applying such therapy to patients.