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野生型p53会削弱对化疗的反应:化不利为有利以保护正常细胞。

Wt p53 impairs response to chemotherapy: make lemonade to spare normal cells.

作者信息

Blagosklonny Mikhail V

机构信息

Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY, USA.

出版信息

Oncotarget. 2012 Jun;3(6):601-7. doi: 10.18632/oncotarget.548.

DOI:10.18632/oncotarget.548
PMID:22802145
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3442293/
Abstract

As published recently in Cancer Cell, p53 impairs the apoptotic response to chemotherapy and clinical outcome in breast cancer. I discuss that, while treating tumors lacking wt p53, this phenomenon can be exploited to protect normal cells from chemotherapy because all normal cells have wt p53. Also, several therapeutic paradigms can be reassessed, including the role of cellular senescence in cancer therapy.

摘要

正如最近发表在《癌细胞》杂志上的文章所述,p53会削弱乳腺癌对化疗的凋亡反应及临床疗效。我认为,在治疗缺乏野生型p53的肿瘤时,这一现象可被利用来保护正常细胞免受化疗影响,因为所有正常细胞都有野生型p53。此外,包括细胞衰老在癌症治疗中的作用在内的几种治疗模式都可重新评估。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c5c/3442293/cc50393b3e4f/oncotarget-03-601-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c5c/3442293/cc50393b3e4f/oncotarget-03-601-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c5c/3442293/cc50393b3e4f/oncotarget-03-601-g001.jpg

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Therapeutic response to CDK4/6 inhibition in breast cancer defined by ex vivo analyses of human tumors.基于对人源肿瘤的体外分析定义乳腺癌对 CDK4/6 抑制的治疗反应。
Cell Cycle. 2012 Jul 15;11(14):2756-61. doi: 10.4161/cc.21195.
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p53-mediated senescence impairs the apoptotic response to chemotherapy and clinical outcome in breast cancer.p53 介导的衰老会损害乳腺癌对化疗的凋亡反应和临床预后。
Cancer Cell. 2012 Jun 12;21(6):793-806. doi: 10.1016/j.ccr.2012.04.027.
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An evaluation of small-molecule p53 activators as chemoprotectants ameliorating adverse effects of anticancer drugs in normal cells.
Cooperation of Nutlin-3a and a Wip1 inhibitor to induce p53 activity.
Nutlin-3a与Wip1抑制剂协同诱导p53活性。
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Mdm2 inhibition confers protection of p53-proficient cells from the cytotoxic effects of Wee1 inhibitors.Mdm2抑制可使p53功能正常的细胞免受Wee1抑制剂的细胞毒性作用。
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Exploiting replicative stress to treat cancer.利用复制压力治疗癌症。
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Deregulation of the EGFR/PI3K/PTEN/Akt/mTORC1 pathway in breast cancer: possibilities for therapeutic intervention.乳腺癌中表皮生长因子受体/磷脂酰肌醇-3激酶/磷酸酶和张力蛋白同源物/蛋白激酶B/哺乳动物雷帕霉素靶蛋白复合物1信号通路的失调:治疗干预的可能性
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