Edwards Sara J, Dix Brett R, Myers Colleen J, Dobson-Le Deirdre, Huschtscha Lily, Hibma Merilyn, Royds Janice, Braithwaite Antony W
Departments of Pathology, University of Otago, Dunedin, New Zealand.
J Virol. 2002 Dec;76(24):12483-90. doi: 10.1128/jvi.76.24.12483-12490.2002.
The adenovirus mutant ONYX-015 is in phase III clinical trials as a novel antitumor therapy. Its apparent efficacy is thought to be due to its ability to replicate selectively in tumor cells defective in the signaling pathway for p53. Recent data have shown that p14(ARF), a positive regulator of p53, inhibits ONYX-015 replication in cells with a wild-type p53, a phenotype that characterizes normal cells. We, however, found that ONYX-015 activates p53 in tumor cells and in normal cells and that this can occur without p14(ARF) induction. We also show that ONYX-015 is not attenuated in cells with functional p53, whether or not p14(ARF) is expressed, and that where attenuation does occur, it is cell type specific.
腺病毒突变体ONYX - 015作为一种新型抗肿瘤疗法正处于III期临床试验阶段。其明显的疗效被认为归因于它能够在p53信号通路有缺陷的肿瘤细胞中选择性复制。最近的数据表明，p53的正向调节因子p14(ARF)可抑制ONYX - 015在具有野生型p53的细胞（这是正常细胞的一种表型特征）中的复制。然而，我们发现ONYX - 015可在肿瘤细胞和正常细胞中激活p53，且这一过程可不依赖p14(ARF)的诱导。我们还表明，无论p14(ARF)是否表达，ONYX - 015在具有功能性p53的细胞中都不会减毒，而在确实发生减毒的情况下，它具有细胞类型特异性。
