Cyclin-dependent kinase inhibitors as potential targeted anticancer agents

被引：55

作者：

Diaz-Padilla, Ivan ^{[1
]}

Siu, Lillian L. ^{[2
]}

Duran, Ignacio ^{[1
]}

机构：

[1] Ctr Integral Oncol Clara Campal, Dept Med Oncol, Madrid 28050, Spain

[2] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada

来源：

INVESTIGATIONAL NEW DRUGS | 2009年 / 27卷 / 06期

关键词：

Cell-cycle; Cyclin-dependent kinase; Flavopiridol; Targeted therapies; CDK inhibitors; PHASE-I TRIAL; CHRONIC LYMPHOCYTIC-LEUKEMIA; ADVANCED SOLID TUMORS; CELL LUNG-CANCER; HEALTHY MALE-VOLUNTEERS; R-ROSCOVITINE; SELICICLIB CYC202; REFRACTORY NEOPLASMS; MULTIPLE-MYELOMA; CLINICAL-TRIALS;

D O I：

10.1007/s10637-009-9236-6

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Cyclin-dependent kinases (CDKs) are core components of the cell cycle machinery that govern the transition between phases during cell cycle progression. Genes involved in cell cycle are frequently mutated in human cancer and deregulated CDK activity represents a hallmark of malignancy. This knowledge provides a rationale for regarding CDKs and their associated molecules as potential targets for new drug development in anticancer research. The present article will review the most relevant CDK inhibitors with emphasis on the newer molecules in clinical development and the biological rationale of this therapeutic approach.

引用

页码：586 / 594

页数：9

共 59 条

[1] Phase II study of flavopiridol in patients with advanced colorectal cancer [J].

Aklilu, M ;

Kindler, HL ;

Donehower, RC ;

Mani, S ;

Vokes, EE .

ANNALS OF ONCOLOGY, 2003, 14 (08) :1270-1273

[2] Gene amplification and overexpression of CDK4 in sporadic breast carcinomas is associated with high tumor cell proliferation [J].

An, HX ;

Beckmann, MW ;

Reifenberger, G ;

Bender, HG ;

Niederacher, D .

AMERICAN JOURNAL OF PATHOLOGY, 1999, 154 (01) :113-118

[3] A phase I trial of the selective oral cyclin-dependent kinase inhibitor seliciclib (CYC202; R-Roscovitine), administered twice daily for 7 days every 21 days [J].

Benson, C. ;

White, J. ;

De Bono, J. ;

O'Donnell, A. ;

Raynaud, F. ;

Cruickshank, C. ;

McGrath, H. ;

Walton, M. ;

Workman, P. ;

Kaye, S. ;

Cassidy, J. ;

Gianella-Borradori, A. ;

Judson, I. ;

Twelves, C. .

BRITISH JOURNAL OF CANCER, 2007, 96 (01) :29-37

[4] N-&-N, a new class of cell death-inducing kinase inhibitors derived from the purine roscovitine [J].

Bettayeb, Karima ;

Sallam, Hatem ;

Ferandin, Yoan ;

Popowycz, Florence ;

Fournet, Guy ;

Hassan, Moustapha ;

Echalier, Aude ;

Bernard, Philippe ;

Endicott, Jane ;

Joseph, Benoit ;

Meijer, Laurent .

MOLECULAR CANCER THERAPEUTICS, 2008, 7 (09) :2713-2724

[5] Phase 1 trial of flavopiridol combined with cisplatin or carboplatin in patients with advanced malignancies with the assessment of pharmacokinetic and pharmacodynamic end points [J].

Bible, KC ;

Lensing, JL ;

Nelson, SA ;

Lee, YK ;

Reid, JM ;

Ames, MM ;

Isham, CR ;

Piens, J ;

Rubin, SL ;

Rubin, J ;

Kaufmann, SH ;

Atherton, PJ ;

Sloan, JA ;

Daiss, MK ;

Adjei, AA ;

Erlichman, C .

CLINICAL CANCER RESEARCH, 2005, 11 (16) :5935-5941

[6] Flavopiridol, an inhibitor of transcription - Implications, problems and solutions [J].

Blagosklonny, MV .

CELL CYCLE, 2004, 3 (12) :1537-1542

[7] Phase II trial of flavopiridol, a cyclin dependent kinase inhibitor, in untreated metastatic malignant melanoma [J].

Burdette-Radoux, S ;

Tozer, RG ;

Lohmann, RC ;

Quirt, I ;

Ernst, DS ;

Walsh, W ;

Wainman, N ;

Colevas, AD ;

Eisenhauer, EA .

INVESTIGATIONAL NEW DRUGS, 2004, 22 (03) :315-322

[8]

Busby EC, 2000, CANCER RES, V60, P2108

[9] Flavopiridol induces apoptosis in chronic lymphocytic leukemia cells via activation of caspase-3 without evidence of bcl-2 modulation or dependence on functional p53 [J].

Byrd, JC ;

Shinn, C ;

Waselenko, JK ;

Fuchs, EJ ;

Lehman, TA ;

Nguyen, PL ;

Flinn, IW ;

Diehl, LF ;

Sausville, E ;

Grever, MR .

BLOOD, 1998, 92 (10) :3804-3816

[10] Flavopiridol administered using a pharmacologically derived schedule is associated with marked clinical efficacy in refractory, genetically high-risk chronic lymphocytic leukemia [J].

Byrd, John C. ;

Lin, Thomas S. ;

Dalton, James T. ;

Wu, Di ;

Phelps, Mitch A. ;

Fischer, Beth ;

Moran, Mollie ;

Blum, Kristie A. ;

Rovin, Brad ;

Brooker-McEldowney, Michelle ;

Broering, Sarah ;

Schaaf, Larry J. ;

Johnson, Amy J. ;

Lucas, David M. ;

Heerema, Nyla A. ;

Lozanski, Gerard ;

Young, Donn C. ;

Suarez, Jose-Ramon ;

Colevas, A. Dimitrios ;

Grever, Michael R. .

BLOOD, 2007, 109 (02) :399-404

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