Soddu S, Sacchi A
Molecular Oncogenesis Laboratory, Regina Elena Cancer Institute, CRS, Rome, Italy.
Cytokines Cell Mol Ther. 1998 Sep;4(3):177-85.
Initially described as an oncogene, at the end of the 1980s, the wild-type p53 gene (TP53) was later shown to be capable of suppressing the proliferation of transformed cells. In the following years, an increasing number of studies demonstrated that intact p53 function is essential for the maintenance of the non-tumorigenic phenotype of cells. Indeed, functional inactivation of the p53 protein is one of the most common alterations observed in human cancers. More recently, it has been shown that inactivation of the TP53 tumor suppressor gene may lead to radioresistant and chemoresistant tumors, possibly by the induction of apoptosis-resistant phenotypes. Finally, a large number of in vitro and in vivo transduction experiments have demonstrated that exogenous TP53 overexpression can suppress the transformed phenotype of many cell types by inducing growth arrest, apoptosis or cell differentiation. All of these findings have rendered p53 a potentially helpful target for the therapy of many types of human cancers. In this review we shall discuss the different approaches to p53-related cancer therapy that have been proposed on the basis of this large number of experimental studies, and we shall try to dissect the biological questions that are still open and need to be clarified to improve p53-based therapy.
野生型p53基因（TP53）最初被描述为一种癌基因，到20世纪80年代末，后来发现它能够抑制转化细胞的增殖。在随后的几年里，越来越多的研究表明，完整的p53功能对于维持细胞的非致瘤表型至关重要。事实上，p53蛋白的功能失活是人类癌症中最常见的改变之一。最近，研究表明TP53肿瘤抑制基因的失活可能导致肿瘤产生放射抗性和化学抗性，这可能是通过诱导抗凋亡表型实现的。最后，大量的体外和体内转导实验表明，外源性TP53过表达可以通过诱导生长停滞、凋亡或细胞分化来抑制多种细胞类型的转化表型。所有这些发现使p53成为多种人类癌症治疗的潜在有用靶点。在这篇综述中，我们将讨论基于大量实验研究提出的与p53相关的癌症治疗的不同方法，并试图剖析仍然存在且需要澄清以改进基于p53的治疗的生物学问题。
