Lønning Per E, Knappskog Stian
Breast Cancer Res. 2012 Nov 6;14(6):325. doi: 10.1186/bcr3326.
The effect of TP53 mutations on chemosensitivity in breast cancer is a controversial issue. In an elegant paper in Cancer Cell, Jackson and colleagues report wtp53 protein to block anti-tumour effects of doxorubicin treatment in mice. p53 did so by inducing senescence, thereby preventing mitotic catastrophy and subsequent cell death. In contrast, while TP53 mutations have shown to predict response to cyclophosphamide high dose therapy, mutations in general have been associated with anthracycline resistance in human breast cancers. The challenging results from Jackson and colleagues' study elucidate a new hypothesis and suggest directions for future translational research in human breast cancer.
TP53突变对乳腺癌化疗敏感性的影响是一个有争议的问题。在《癌细胞》杂志上发表的一篇精彩论文中,杰克逊及其同事报告称,野生型p53蛋白会阻断阿霉素治疗对小鼠的抗肿瘤作用。p53通过诱导衰老来实现这一点,从而防止有丝分裂灾难及随后的细胞死亡。相比之下,虽然TP53突变已被证明可预测对高剂量环磷酰胺治疗的反应,但一般来说,突变与人类乳腺癌中的蒽环类耐药有关。杰克逊及其同事研究得出的具有挑战性的结果阐明了一个新假说,并为未来人类乳腺癌的转化研究指明了方向。