Cell Cycle Regulation Group, Department of Medicine, Institute of Cancer Research, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
Future Med Chem. 2018 Apr 1;10(7):755-777. doi: 10.4155/fmc-2017-0175. Epub 2018 Mar 23.
p53 protein, a product of the TP53 tumor suppressor gene, controls the cellular genome's integrity and is an important regulator of cell cycling, proliferation, apoptosis and metabolism. Mutations of TP53 or inactivation of its gene product are among the first events initiating malignant transformation. The consequent loss of control over the cell cycle, resulting in accelerated cell proliferation and facilitating metabolic reprogramming, gives the initiated (premalignant) cells numerous advantages over healthy cells. Interestingly, p53 status is not only an important marker in cancer diagnosis; it has also become a promising target of personalized therapy. Depending on the TP53 status different therapeutic options have been developed. (Re)-activation of p53 functionality in cancer cells offers promising new alternatives to existing oncological therapies.
p53 蛋白是 TP53 肿瘤抑制基因的产物，它控制着细胞基因组的完整性，是细胞周期、增殖、凋亡和代谢的重要调节因子。TP53 基因突变或其基因产物失活是引发恶性转化的最初事件之一。随之而来的对细胞周期的失控，导致细胞增殖加速，并促进代谢重编程，使起始（癌前）细胞相对于健康细胞具有许多优势。有趣的是，p53 状态不仅是癌症诊断中的一个重要标志物，而且也成为了个性化治疗的一个有前途的靶点。根据 TP53 状态，已经开发出不同的治疗选择。在癌细胞中重新激活 p53 功能为现有肿瘤治疗提供了有前途的新选择。
