Staples O D, Steele R J C, Lain S
Department of Surgery and Molecular Oncology, Ninewells Hospital and Medical School University of Dundee.
Surgeon. 2008 Aug;6(4):240-3. doi: 10.1016/s1479-666x(08)80034-0.
Since the discovery of p53, a vast wealth of knowledge on its function and regulation has been accumulated. It is known that it is a key tumour suppressor and that its function is lost in many types of cancers, either by mutation or by excessive negative regulation. Recently, several discoveries have re-energised P53 as a therapeutic target as it has been shown that reintroduction of functional p53 into tumours has a therapeutic benefit. These encouraging results clearly justify the search for small molecules that diminish negative regulation of P53 in tumour cells, where P53 is not mutated as well as compounds that reactivate mutant P53. Important findings have been made to deal with both situations. Additionally, some of the small molecules identified may also help reduce the side effects of commonly used cancer therapeutics. These studies are still in their infancy and require further therapeutic validation, but the future appears bright for finally harnessing p53's tumour suppressing ability.
自p53被发现以来，关于其功能和调控的知识已大量积累。已知它是一种关键的肿瘤抑制因子，并且在许多类型的癌症中，其功能会因突变或过度的负调控而丧失。最近，一些发现使p53作为治疗靶点重新受到关注，因为已表明将功能性p53重新引入肿瘤具有治疗益处。这些令人鼓舞的结果显然为寻找能减少肿瘤细胞中p53负调控的小分子以及重新激活突变型p53的化合物提供了依据。在应对这两种情况方面均已取得重要发现。此外，所鉴定出的一些小分子还可能有助于减轻常用癌症治疗药物的副作用。这些研究仍处于初期阶段，需要进一步的治疗验证，但最终利用p53的肿瘤抑制能力的前景似乎十分光明。
