A WEE1 family business: regulation of mitosis, cancer progression, and therapeutic target.
A WEE1 family business: regulation of mitosis, cancer progression, and therapeutic target.
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DOI：
10.1186/s13045-020-00959-2
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发表时间：
2020-09-21
影响因子：
28.5
通讯作者：
Simonetti G
中科院分区：
文献类型：
--
作者：
Ghelli Luserna di Rorà A;Cerchione C;Martinelli G;Simonetti G
DNA损伤反应（DDR）途径的抑制在癌症治疗中最近引起了人们的兴趣，并且已经开发了不同的DDR抑制剂。其中，最有前途的是针对 WEE1 激酶家族，该家族在非恶性和癌细胞的细胞周期调节以及 DNA 损伤识别和修复中发挥着至关重要的作用。这篇综述概述并讨论了 WEE1/PKMYT1 在细胞周期和 DNA 损伤修复中生物学功能的最新发现，重点关注它们作为非恶性细胞中的肿瘤抑制基因和癌细胞中的假癌基因的双重作用。我们在此报告有关 WEE1/PKMYT1 激酶在血液肿瘤和实体瘤中分子和功能改变的可用数据。此外，我们总结了 36 种化疗/放疗药物的临床前信息，特别是它们对细胞周期检查点和细胞 WEE1/PKMYT1 依赖性反应的影响。最后，本综述概述了关于 WEE1/PKMYT1 抑制剂在单一疗法以及与化疗/放疗药物或目前使用或正在评估的其他选择性抑制剂联合治疗癌症患者中的疗效的最重要的临床前和临床数据。
The inhibition of the DNA damage response (DDR) pathway in the treatment of cancer has recently gained interest, and different DDR inhibitors have been developed. Among them, the most promising ones target the WEE1 kinase family, which has a crucial role in cell cycle regulation and DNA damage identification and repair in both nonmalignant and cancer cells. This review recapitulates and discusses the most recent findings on the biological function of WEE1/PKMYT1 during the cell cycle and in the DNA damage repair, with a focus on their dual role as tumor suppressors in nonmalignant cells and pseudo-oncogenes in cancer cells. We here report the available data on the molecular and functional alterations of WEE1/PKMYT1 kinases in both hematological and solid tumors. Moreover, we summarize the preclinical information on 36 chemo/radiotherapy agents, and in particular their effect on cell cycle checkpoints and on the cellular WEE1/PKMYT1-dependent response. Finally, this review outlines the most important pre-clinical and clinical data available on the efficacy of WEE1/PKMYT1 inhibitors in monotherapy and in combination with chemo/radiotherapy agents or with other selective inhibitors currently used or under evaluation for the treatment of cancer patients.
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影响因子：
3.2
作者：
Caldwell, J. Timothy;Edwards, Holly;Buck, Steven A.;Ge, Yubin;Taub, Jeffrey W.
通讯作者：
Taub, Jeffrey W.
DOI：
10.1158/1078-0432.ccr-14-0720
发表时间：
2014-08-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Bauman JE;Chung CH
通讯作者：
Chung CH
影响因子：
28.2
作者：
Aarts, Marieke;Sharpe, Rachel;Turner, Nicholas C.
通讯作者：
Turner, Nicholas C.
影响因子：
15.9
作者：
Bukhari, Amirali B.;Lewis, Cody W.;Gamper, Armin M.
通讯作者：
Gamper, Armin M.
影响因子：
10.1
作者：
Chaudhuri, Leena;Vincelette, Nicole D.;Tibes, Raoul
通讯作者：
Tibes, Raoul