Istituto per l'Endocrinologia e l'Oncologia Sperimentale, Consiglio Nazionale delle Ricerche (CNR), Via S. Pansini, 5, 80131 Naples, Italy.
Dipartimento di Medicina Molecolare e Biotecnologie Mediche, University of Naples Federico II, Via S. Pansini, 5, 80131 Naples, Italy.
Int J Mol Sci. 2024 Oct 25;25(21):11464. doi: 10.3390/ijms252111464.
The dysregulated NF-κB basal activity is a common feature of human thyroid carcinomas, especially in poorly differentiated or undifferentiated forms that, even if rare, are often resistant to standard therapies, and, therefore, are uncurable. Despite the molecular mechanisms leading to NF-κB activation in thyroid cancer being only partially understood, during the last few years, it has become clear that NF-κB contributes in different ways to the oncogenic potential of thyroid neoplastic cells. Indeed, it enhances their proliferation and viability, promotes their migration to and colonization of distant organs, and fuels their microenvironment. In addition, NF-κB signaling plays an important role in cancer stem cells from more aggressive thyroid carcinomas. Interfering with the different upstream and/or downstream pathways that drive NF-κB activity in thyroid neoplastic cells is an attractive strategy for the development of novel therapeutic drugs capable of overcoming the therapy resistance of advanced thyroid carcinomas. This review focuses on the recent findings about the key functions of NF-κB in thyroid cancer and discusses the potential implications of targeting NF-κB in advanced thyroid carcinomas.
NF-κB 基础活性失调是人类甲状腺癌的一个共同特征,特别是在分化不良或未分化的形式中,尽管这种情况很少见,但往往对标准治疗具有抗药性,因此无法治愈。尽管导致甲状腺癌中 NF-κB 激活的分子机制仅部分被理解,但在过去几年中,已经清楚的是,NF-κB 以不同的方式促进甲状腺肿瘤细胞的致癌潜力。实际上,它增强了它们的增殖和活力,促进了它们向远处器官的迁移和定植,并为它们的微环境提供了燃料。此外,NF-κB 信号在更具侵袭性的甲状腺癌中的癌症干细胞中发挥着重要作用。干扰驱动甲状腺肿瘤细胞中 NF-κB 活性的不同上游和/或下游途径是开发能够克服晚期甲状腺癌治疗抵抗性的新型治疗药物的有吸引力的策略。这篇综述重点介绍了 NF-κB 在甲状腺癌中的关键功能的最新发现,并讨论了针对晚期甲状腺癌中 NF-κB 的潜在意义。