Drugging cell cycle kinases in cancer therapy

被引:77
作者
Blagden, S
de Bono, J
机构
[1] Royal Marsden Hosp, Inst Canc Res, Ctr Canc Therapeut, Sutton SM2 5PT, Surrey, England
[2] Inst Canc Res, Sutton, Surrey, England
关键词
cyclin dependent kinase inhibitors; aurora; polo-like kinase;
D O I
10.2174/1389450053765824
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Cell cycle kinases are comprised of cyclin-dependent kinases (Cdks), non-Cdk kinases such as Plk-1 and Aurora and checkpoint proteins such as Chk1 and Chk2. Though ubiquitous to dividing cells, many cell cycle kinases are amplified or over-expressed in malignancy and are potential targets for anti-cancer therapies. Cdk inhibiting drugs (such as flavopiridol, UCN-01, E7070, R-Roscovitine and BMS-387032) have shown preclinical and clinical anticancer activity. However, many of these agents are promiscuous and undiscerning, targeting other non-cell cycle kinases and affecting normal cells, thereby causing significant toxicity. To overcome this, a new generation of Cdk inhibitors are in development with greater target specificity, as well as others that inhibit non-Cdk cell cycle kinases, both directly and indirectly. The outcome of early clinical trials involving these agents is awaited, but these certainly represent a promising new area of anticancer drug development.
引用
收藏
页码:325 / 335
页数:11
相关论文
共 50 条
[21]   Cell-Active, Arginine-Targeting Irreversible Covalent Inhibitors for Non-Kinases and Kinases [J].
Chen, Peng ;
Wang, Lu ;
Wang, Xuan ;
Sun, Jie ;
Miao, Fengfei ;
Wang, Zuqin ;
Yang, Fang ;
Xiang, Menghua ;
Gu, Mingxi ;
Li, Shengrong ;
Zhang, Jianzhong ;
Yuan, Peiyan ;
Lu, Xiaoyun ;
Zhang, Zhi-Min ;
Gao, Liqian ;
Yao, Shao Q. .
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2025, 64 (13)
[22]   Phosphatases and kinases regulating CDC25 activity in the cell cycle: clinical implications of CDC25 overexpression and potential treatment strategies [J].
Sur, Swastika ;
Agrawal, Devendra K. .
MOLECULAR AND CELLULAR BIOCHEMISTRY, 2016, 416 (1-2) :33-46
[23]   Constitutive expression of functionally active cyclin-dependent kinases and their binding partners suggests noncanonical functions of cell cycle regulators in differentiated neurons [J].
Schmetsdorf, Stefanie ;
Gaertner, Ulrich ;
Arendt, Thomas .
CEREBRAL CORTEX, 2007, 17 (08) :1821-1829
[24]   Absence of primary cilia in cell cycle-arrested human breast cancer cells [J].
Nobutani, Kentaro ;
Shimono, Yohei ;
Yoshida, Midori ;
Mizutani, Kiyohito ;
Minami, Akihiro ;
Kono, Seishi ;
Mukohara, Toru ;
Yamasaki, Takashi ;
Itoh, Tomoo ;
Takao, Shintaro ;
Minami, Hironobu ;
Azuma, Takeshi ;
Takai, Yoshimi .
GENES TO CELLS, 2014, 19 (02) :141-152
[25]   Coupling the cell cycle to development [J].
Budirahardja, Yemima ;
Goenczy, Pierre .
DEVELOPMENT, 2009, 136 (17) :2861-2872
[26]   Coordination of the Cell Cycle in Trypanosomes [J].
Wheeler, Richard J. ;
Gull, Keith ;
Sunter, Jack D. .
ANNUAL REVIEW OF MICROBIOLOGY, VOL 73, 2019, 73 :133-154
[27]   Implications of endoplasmic reticulum stress, the unfolded protein response and apoptosis for molecular cancer therapy. Part II: targeting cell cycle events, caspases, NF-κB and the proteasome [J].
Hiss, Donavon C. ;
Gabriels, Gary A. .
EXPERT OPINION ON DRUG DISCOVERY, 2009, 4 (09) :907-921
[28]   Removing the brakes to cardiomyocyte cell cycle [J].
Di Stefano, Valeria ;
Martelli, Fabio .
CELL CYCLE, 2011, 10 (08) :1176-1177
[29]   Cell cycle inhibitors for the treatment of NSCLC [J].
Shcherba, Marina ;
Liang, Yuanxin ;
Fernandes, David ;
Perez-Soler, Roman ;
Cheng, Haiying .
EXPERT OPINION ON PHARMACOTHERAPY, 2014, 15 (07) :991-1004
[30]   Epithelial integrity and cell division: Concerted cell cycle control [J].
Ragkousi, Katerina ;
Gibson, Matthew C. .
CELL CYCLE, 2018, 17 (04) :399-400