Vazquez Alexei, Bond Elisabeth E, Levine Arnold J, Bond Gareth L
The Institute for Advanced Study, Einstein Drive, Princeton, New Jersey, 08540, USA.
Nat Rev Drug Discov. 2008 Dec;7(12):979-87. doi: 10.1038/nrd2656.
The p53 pathway has been shown to mediate cellular stress responses; p53 can initiate DNA repair, cell-cycle arrest, senescence and, importantly, apoptosis. These responses have been implicated in an individual's ability to suppress tumour formation and to respond to many types of cancer therapy. Here we focus on how best to use knowledge of this pathway to tailor current therapies and develop novel ones. Studies of the genetics of p53 pathway components - in particular p53 itself and its negative regulator MDM2 - in cancer cells has proven useful in the development of targeted therapies. Furthermore, inherited single nucleotide polymorphisms in p53 pathway genes could serve a similar purpose.
p53信号通路已被证明可介导细胞应激反应；p53能够启动DNA修复、细胞周期停滞、衰老，以及重要的细胞凋亡过程。这些反应与个体抑制肿瘤形成的能力以及对多种癌症治疗的反应有关。在此，我们聚焦于如何最好地利用该信号通路的知识来优化现有疗法并开发新疗法。对癌细胞中p53信号通路组分——尤其是p53自身及其负调控因子MDM2——的遗传学研究已证明在开发靶向疗法方面很有用。此外，p53信号通路基因中的遗传性单核苷酸多态性也可能有类似作用。
