Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Neoplasia. 2021 Feb;23(2):189-196. doi: 10.1016/j.neo.2020.12.006. Epub 2020 Dec 26.
Tumor necrosis factor (TNF) and its receptors are widely expressed in non-small cell lung cancer (NSCLC). TNF has an established role in inflammation and also plays a key role in inflammation-induced cancer. TNF can induce cell death in cancer cells and has been used as a treatment in certain types of cancer. However, TNF is likely to play an oncogenic role in multiple types of cancer, including NSCLC. TNF is a key activator of the transcription factor NF-κB. NF-κB, in turn, is a key effector of TNF in inflammation-induced cancer. Data from The Cancer Genome Atlas database suggest that TNF could be a biomarker in NSCLC and indicate a complex role for TNF and its receptors in NSCLC. Recent studies have reported that TNF is rapidly upregulated in NSCLC in response to targeted treatment with epidermal growth factor receptor (EGFR) inhibition, and this upregulation leads to NF-κB activation. The TNF upregulation and consequent NF-κB activation play a key role in mediating both primary and secondary resistance to EGFR inhibition in NSCLC, and a combined inhibition of EGFR and TNF can overcome therapeutic resistance in experimental models. TNF may mediate the toxic side effects of immunotherapy and may also modulate resistance to immune checkpoint inhibitors. Drugs inhibiting TNF are widely used for the treatment of various inflammatory and rheumatologic diseases and could be quite useful in combination with targeted therapy of NSCLC and other cancers.
肿瘤坏死因子（TNF）及其受体在非小细胞肺癌（NSCLC）中广泛表达。TNF 在炎症中具有既定作用，并且在炎症诱导的癌症中也起着关键作用。TNF 可以诱导癌细胞死亡，并已被用于某些类型癌症的治疗。然而，TNF 可能在多种类型的癌症中发挥致癌作用，包括 NSCLC。TNF 是转录因子 NF-κB 的关键激活剂。NF-κB 反过来又是 TNF 在炎症诱导的癌症中的关键效应因子。来自癌症基因组图谱数据库的数据表明，TNF 可能是 NSCLC 的生物标志物，并表明 TNF 及其受体在 NSCLC 中具有复杂的作用。最近的研究报告称，TNF 在 NSCLC 中对表皮生长因子受体（EGFR）抑制的靶向治疗迅速上调，这种上调导致 NF-κB 激活。TNF 的上调和随之而来的 NF-κB 激活在介导 NSCLC 中 EGFR 抑制的原发性和继发性耐药中起着关键作用，并且 EGFR 和 TNF 的联合抑制可以克服实验模型中的治疗耐药性。TNF 可能介导免疫疗法的毒性副作用，并且还可能调节对免疫检查点抑制剂的耐药性。抑制 TNF 的药物广泛用于治疗各种炎症性和风湿性疾病，并且与 NSCLC 和其他癌症的靶向治疗联合使用可能非常有用。
