Cortés Sempere María, Rodríguez Fanjul Vanesa, Sánchez Pérez Isabel, Perona Rosario
Instituto de Investigaciones Biomédicas CSIC/UAM, Translational Oncology Unit, Centro de Investigación Biomédica en Red para Enfermedades Raras, Madrid, Spain.
Clin Transl Oncol. 2008 Mar;10(3):143-7. doi: 10.1007/s12094-008-0171-3.
The nuclear factor kappa B (NFkappaB) signalling pathway regulates the expression of hundreds of genes that are involved in different cellular processes such as cell proliferation, survival, stress responses, cellular immunity and inflammation. Its aberrant regulation is involved in several pathologies, but its relevance in cellular transformation and cancer development has been extensively studied. Mutations in the core components of NFkappaB as well as in the cellular machinery that regulates its activation have been found in many types of tumours. On the other hand, its role in promoting cell survival is an important obstacle in many cancer therapies. The development of chemical inhibitors that block NFkappaB activation acting either directly on IKKs or on the proteosome machinery has shown antitumour and proapoptotic activity both in preclinical and clinical studies.
核因子κB(NFκB)信号通路调控着数百个参与不同细胞过程的基因的表达,这些细胞过程包括细胞增殖、存活、应激反应、细胞免疫和炎症。其异常调控涉及多种病理状况,但其在细胞转化和癌症发展中的相关性已得到广泛研究。在许多类型的肿瘤中都发现了NFκB核心成分以及调节其激活的细胞机制中的突变。另一方面,其在促进细胞存活中的作用是许多癌症治疗中的一个重要障碍。在临床前和临床研究中,直接作用于IKK或蛋白酶体机制的阻断NFκB激活的化学抑制剂的开发已显示出抗肿瘤和促凋亡活性。