G2 checkpoint abrogation and checkpoint kinase-1 targeting in the treatment of cancer.
G2 checkpoint abrogation and checkpoint kinase-1 targeting in the treatment of cancer.
复制标题
DOI：
10.1038/sj.bjc.6604208
复制
发表时间：
2008-02-12
影响因子：
8.8
通讯作者：
Britten, C. D.
中科院分区：
文献类型：
--
作者：
Bucher, N.;Britten, C. D.
严格的质量控制步骤，称为检查点，严格调节细胞周期的进展。DNA损伤化疗和放疗激活功能性细胞检查点。这些检查点可以促进DNA修复并促进未修复细胞的细胞死亡。至少有三个DNA损伤检查点-在G1/S，S和G2/M -以及有丝分裂纺锤体检查点。大多数癌细胞在肿瘤抑制因子和/或致癌基因中含有突变，这会损害某些细胞检查点。抑制剩余的细胞检查点-特别是在癌细胞暴露于化疗和/或辐射之后-允许细胞死亡，这是目前在癌症治疗中采用的策略。随着我们对细胞周期调控的了解越来越多，已经开发了许多化合物来抑制特定的检查点组分，特别是在G2/M转换。一个这样的靶标是检查点激酶-1（Chk 1）。我们在这里审查的细胞周期的分子框架，针对Chk 1的基本原理，与Chk 1抑制剂的发展相关的临床前概念，和Chk 1抑制剂的疗效和安全性结果，现在在I/II期试验。
Rigorous quality control steps, termed checkpoints, tightly regulate progression through the cell cycle. DNA-damaging chemotherapy and radiation activate functional cellular checkpoints. These checkpoints can facilitate DNA repair and promote cell death in unrepaired cells. There are at least three DNA damage checkpoints – at G1/S, S, and G2/M – as well as a mitotic spindle checkpoint. Most cancer cells harbour mutations in tumour suppressors and/or oncogenes, which impair certain cell checkpoints. Inhibiting the remaining cell checkpoints – particularly after exposure of cancer cells to chemotherapy and/or radiation – allows cell death, a strategy now being employed in cancer therapeutics. With our increasing knowledge of cell cycle regulation, many compounds have been developed to inhibit specific checkpoint components, particularly at the G2/M transition. One such target is checkpoint kinase-1 (Chk1). We review here the molecular framework of the cell cycle, the rationale for targeting Chk1, the preclinical concepts related to the development of Chk1 inhibitors, and the efficacy and safety results from Chk1 inhibitors now in phase I/II trials.
登录
查看更多内容
影响因子：
30.8
作者：
Falck, J;Petrini, JHJ;Bartek, J
通讯作者：
Bartek, J
影响因子：
45.3
作者：
Kortmansky, J;Shah, MA;Schwartz, GK
通讯作者：
Schwartz, GK
影响因子：
16
作者：
Manke, IA;Nguyen, A;Yaffe, MB
通讯作者：
Yaffe, MB
DOI：
10.1073/pnas.79.9.2942
发表时间：
1982-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
LAU, CC;PARDEE, AB
通讯作者：
PARDEE, AB
影响因子：
11.2
作者：
Hickson, I;Yan, Z;Smith, GCM
通讯作者：
Smith, GCM