Dana-Farber癌症研究所的研究人员发现了一种新的癌症治疗方法，即通过某种药物损伤癌细胞DNA同时阻止癌细胞进行自我修复，使癌细胞自我毁灭从而达到治疗癌症的目的。这项研究发表在8月14日的Molecular Cell杂志上。
据研究人员Shapiro介绍，正常细胞的DNA损伤修复过程对这类DNA修复阻断药物(repair-blocking drugs)具有较低的敏感性。这意味着修复阻断药物能够选择性阻断癌细胞DNA修复，并对正常细胞无影响。
机体对发生DNA损伤的细胞有两种处理方式。一种为细胞程序性死亡(programmed cell death)，即凋亡。另一种可以通过检验点蛋白(checkpoint proteins)发出的信号是细胞进入细胞周期阻滞(cell cycle arrest)。
当细胞的DNA发生损伤时，细胞会引发一系列的检验点级联反应（checkpoint cascade），cdk1和cdk2这两种主要的检验点蛋白，发出信号阻止细胞周期反应，并在DNA损伤位点进行DNA修复。而修复阻断药物的作用是压制检验点蛋白发出的信号，从而防止化疗损伤的癌细胞进行自我修复。
在临床试验中，科学家利用抑制药物阻断cdk信号。这些药物能引起损伤细胞绕过检验点的控制继续生长，分裂和死亡。研究人员在该研究报告中还提到了cdk抑制剂作用的分子机制。(生物谷Bioon.com)
生物谷推荐原始出处：
Molecular Cell, Volume 35, Issue 3, 327-339, 14 August 2009.doi:10.1016/j.molcel.2009.06.036
Cdk1 Participates in BRCA1-Dependent S Phase Checkpoint Control in Response to DNA Damage
Neil Johnson1,Dongpo Cai1,Richard D. Kennedy2,8,Shailja Pathania3,Mansi Arora4,5,Yu-Chen Li1,Alan D. D'Andrea6,Jeffrey D. Parvin4,5and Geoffrey I. Shapiro1,7,*
1 Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA
2 Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA
3 Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA
4 Department of Biomedical Informatics , Ohio State University, Columbus, OH 43210, USA
5 The Comprehensive Cancer Center, Ohio State University, Columbus, OH 43210, USA
6 Department of Pediatrics, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
7 Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA
* Corresponding author
Cdk2 and cdk1 are individually dispensable for cell-cycle progression in cancer cell lines because they are able to compensate for one another. However, shRNA-mediated depletion of cdk1 alone or small molecule cdk1 inhibition abrogated S phase cell-cycle arrest and the phosphorylation of a subset of ATR/ATM targets after DNA damage. Loss of DNA damage-induced checkpoint control was caused by a reduction in formation of BRCA1-containing foci. Mutation of BRCA1 at S1497 and S1189/S1191 resulted in loss of cdk1-mediated phosphorylation and also compromised formation of BRCA1-containing foci. Abrogation of checkpoint control after cdk1depletion or inhibition in non-small-cell lung cancer cells sensitized them to DNA-damaging agents. Conversely, reduced cdk1 activity caused more potent G2/M arrest in nontransformed cells and antagonized the response to subsequent DNA damage. Cdk1 inhibition may therefore selectively sensitize BRCA1-proficient cancer cells to DNA-damaging treatments by disrupting BRCA1 function.
