Cell cycle kinases as therapeutic targets for cancer

被引:761
作者
Lapenna, Silvia [1 ,2 ]
Giordano, Antonio [2 ,3 ]
机构
[1] Oncol Res Ctr Mercogliano, Avellino, Italy
[2] Univ Siena, Dept Human Pathol & Oncol, I-53100 Siena, Italy
[3] Temple Univ, Ctr Biotechnol, Sbarro Inst Canc Res & Mol Med, Philadelphia, PA 19122 USA
基金
美国国家卫生研究院;
关键词
SMALL-MOLECULE INHIBITOR; AURORA-B-KINASE; CHRONIC LYMPHOCYTIC-LEUKEMIA; PRB2/P130 SPACER DOMAIN; TUMOR-GROWTH INHIBITOR; ADVANCED SOLID TUMORS; IN-VIVO ACTIVITY; DEPENDENT KINASE; SELECTIVE INHIBITOR; PHASE-I;
D O I
10.1038/nrd2907
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Several families of protein kinases orchestrate the complex events that drive the cell cycle, and their activity is frequently deregulated in hyperproliferative cancer cells. Although several molecules that inhibit cell cycle kinases have been developed and clinically screened as potential anticancer agents, none of these has been approved for commercial use and an effective strategy to specifically control malignant cell proliferation has yet to be established. However, recent genetic and biochemical studies have provided information about the requirement for certain cell cycle kinases by specific tumours and specialized tissue types. Here, we discuss the potential and limitations of established cell cycle kinases as targets in anticancer drug discovery as well as novel strategies for the design of new agents.
引用
收藏
页码:547 / 566
页数:20
相关论文
共 183 条
  • [51] Aurora kinases as anticancer drug targets
    Gautschi, Oliver
    Heighway, Jim
    Mack, Philip C.
    Purnell, Phillip R.
    Lara, Primo N., Jr.
    Gandara, David R.
    [J]. CLINICAL CANCER RESEARCH, 2008, 14 (06) : 1639 - 1648
  • [52] Phase I study of flavopiridol in combination with paclitaxel and carboplatin in patients with non-small-cell lung cancer
    George, Saby
    Kasimis, Basil S.
    Cogswell, Janet
    Schwarzenberger, Paul
    Shapiro, Geoffrey I.
    Fidias, Panos
    Bukowski, Ronald M.
    [J]. CLINICAL LUNG CANCER, 2008, 9 (03) : 160 - 165
  • [53] RB and cell cycle progression
    Giacinti, C.
    Giordano, A.
    [J]. ONCOGENE, 2006, 25 (38) : 5220 - 5227
  • [54] Interaction between the Cdk2/Cyclin a complex and a small molecule derived from the pRb2/p130 spacer domain
    Giordano, Antonio
    Bellacchio, Emanuele
    Bagella, Luigi
    Paggi, Marco G.
    [J]. CELL CYCLE, 2007, 6 (21) : 2591 - 2593
  • [55] Molecular basis of drug resistance in Aurora kinases
    Girdler, Fiona
    Sessa, Fabio
    Patercoli, Simona
    Villa, Fabrizio
    Musacchio, Andrea
    Taylor, Stephen
    [J]. CHEMISTRY & BIOLOGY, 2008, 15 (06): : 552 - 562
  • [56] Proteomic characterization of the angiogenesis inhibitor SU6668 reveals multiple impacts on cellular kinase signaling
    Godl, K
    Gruss, OJ
    Eickhoff, J
    Wissing, J
    Blencke, S
    Weber, M
    Degen, H
    Brehmer, D
    Orfi, L
    Horváth, Z
    Kéri, G
    Müller, S
    Cotten, M
    Ullrich, A
    Daub, H
    [J]. CANCER RESEARCH, 2005, 65 (15) : 6919 - 6926
  • [57] Inhibition of CDK1 as a potential therapy for tumors over-expressing MYC
    Goga, Andrei
    Yang, Dun
    Tward, Aaron D.
    Morgan, David O.
    Bishop, J. Michael
    [J]. NATURE MEDICINE, 2007, 13 (07) : 820 - 827
  • [58] Lining the pockets of kinases and phosphatases
    Gold, Matthew G.
    Barford, David
    Komander, David
    [J]. CURRENT OPINION IN STRUCTURAL BIOLOGY, 2006, 16 (06) : 693 - 701
  • [59] GORGUN G, 2008, 50 ASH ANN M 6 8 DEC
  • [60] Griffiths G, 2008, AACR ANN M 12 16 APR