Hsp90 inhibitors and drug resistance in cancer: the potential benefits of combination therapies of Hsp90 inhibitors and other anti-cancer drugs.
Hsp90 inhibitors and drug resistance in cancer: the potential benefits of combination therapies of Hsp90 inhibitors and other anti-cancer drugs.
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DOI：
10.1016/j.bcp.2011.11.011
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发表时间：
2012-04-15
影响因子：
5.8
通讯作者：
Ruden, Douglas M.
中科院分区：
文献类型：
--
作者：
Lu, Xiangyi;Xiao, Li;Wang, Luan;Ruden, Douglas M.
Hsp90是一种伴侣蛋白，与已知参与细胞周期、信号传导和染色质重塑途径的客户蛋白相互作用。在小鼠肿瘤模型和人类中，Hsp90抑制剂与许多其他药物共同作用或协同作用于实体瘤和白血病的治疗。Hsp90抑制剂可以增强靶向Hsp90客户蛋白的抗癌药物的作用，包括靶向Her2/Erb2B的曲妥珠单抗（赫赛汀™），因为Hsp90抑制剂可以在对药物产生耐药性的癌细胞系中引起药物作用。一项针对Hsp90抑制剂17-AAG和曲妥珠单抗的II期研究显示，这种联合疗法对接受曲妥珠单抗治疗的her2阳性转移性乳腺癌患者具有抗癌活性。在这篇综述中，我们讨论了Hsp90抑制剂与曲妥珠单抗和其他抗癌药物联合使用的结果。我们还讨论了最近来自酵母的研究结果，重点是当Hsp90被抑制时的耐药遗传学，以及这可能对理解遗传变异在治疗人类癌症中的作用的影响。
Hsp90 is a chaperone protein that interacts with client proteins that are known to be in the cell cycle, signaling and chromatin-remodeling pathways. Hsp90 inhibitors act additively or synergistically with many other drugs in the treatment of both solid tumors and leukemias in murine tumor models and humans. Hsp90 inhibitors potentiate the actions of anti-cancer drugs that target Hsp90 client proteins, including trastuzumab (Herceptin™) which targets Her2/Erb2B, as Hsp90 inhibition elicits the drug effects in cancer cell lines that are otherwise resistant to the drug. A Phase II study of the Hsp90 inhibitor 17-AAG and trastuzumab showed that this combination therapy has anticancer activity in patients with HER2-positive metastatic breast cancer progressing on trastuzumab. In this review, we discuss the results of Hsp90 inhibitors in combination with trastuzumab and other cancer drugs. We also discuss recent results from yeast focused on the genetics of drug resistance when Hsp90 is inhibited and the implications that this might have in understanding the effects of genetic variation in treating cancer in humans.
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影响因子：
5.8
作者：
Cristina de Almagro, M.;Selga, Elisabet;Ciudad, Carlos J.
通讯作者：
Ciudad, Carlos J.
影响因子：
--
作者：
Aldana-Masangkay GI;Sakamoto KM
通讯作者：
Sakamoto KM
影响因子：
11.4
作者：
Blagosklonny, MV;Fojo, T;Neckers, LM
通讯作者：
Neckers, LM
DOI：
10.1158/1940-6207.capr-11-0266
发表时间：
2011-07
期刊：
Cancer prevention research (Philadelphia, Pa.)
影响因子：
--
作者：
Athar M;Kopelovich L
通讯作者：
Kopelovich L
影响因子：
3.4
作者：
Beck, Raphael;Pedrosa, Rozangela Curi;Verrax, Julien
通讯作者：
Verrax, Julien