Bertheau Philippe, Espié Marc, Turpin Elisabeth, Lehmann Jacqueline, Plassa Louis-François, Varna Mariana, Janin Anne, de Thé Hugues
Department of Pathology, Hospital St-Louis, APHP and University Paris 7, INSERM U728, Paris, France.
Pathobiology. 2008;75(2):132-9. doi: 10.1159/000123851. Epub 2008 Jun 10.
Despite its central role in the control of apoptosis, senescence and cell cycle arrest, the tumor suppressor protein p53 remains an enigma for its possible role in predicting response to chemotherapy in cancer patients. Many studies remained inconclusive, others showed a better response for tumors with normal p53, and some recent studies showed adverse effects of normal p53 for response to treatment. p53 is not only a powerful pro-apoptotic factor in response to drug-induced DNA damages but also a potential inducer of cell cycle arrest, protecting tumor cells from further cytotoxic damages. Our review describes the classical as well as the more recent concepts. In order to draw definite conclusions, future works should use more reliable methods to assess the TP53 status and should address more homogeneous tumor subpopulations treated with homogeneous chemotherapy regimens.
尽管肿瘤抑制蛋白p53在细胞凋亡、衰老和细胞周期停滞的控制中发挥着核心作用，但其在预测癌症患者化疗反应方面的潜在作用仍是一个谜。许多研究尚无定论，其他研究表明p53正常的肿瘤对化疗反应更好，而一些近期研究显示p53正常对治疗反应有不利影响。p53不仅是对药物诱导的DNA损伤作出反应的强大促凋亡因子，也是细胞周期停滞的潜在诱导因子，可保护肿瘤细胞免受进一步的细胞毒性损伤。我们的综述描述了经典概念以及最新概念。为了得出明确的结论，未来的研究应使用更可靠的方法来评估TP53状态，并应针对接受同类化疗方案治疗的更同质的肿瘤亚群展开研究。
