Cyclin-dependent kinase inhibitors as potential targeted anticancer agents

Investigational New Drugs

Volumn 27, Issue 6, 2009, Pages 586-594

  Diaz Padilla, Ivan ^a   Siu, Lillian L ^b   Duran, Ignacio ^a  

^a Centro Integral Oncologico Clara Campal   (Spain)

^b PRINCESS MARGARET HOSPITAL   (Canada)

Author keywords

CDK inhibitors; Cell cycle; Cyclin dependent kinase; Flavopiridol; Targeted therapies

Indexed keywords

6 ACETYL 8 CYCLOPENTYL 5 METHYL 2 [5 (1 PIPERAZINYL) 2 PYRIDINYLAMINO] 8H PYRIDO[2,3 D]PYRIMIDIN 7 ONE; 7 HYDROXYSTAUROSPORINE; ANTINEOPLASTIC AGENT; AZD 5438; BEVACIZUMAB; CYCLIN DEPENDENT KINASE; CYCLIN DEPENDENT KINASE INHIBITOR; DOCETAXEL; FLAVOPIRIDOL; IRINOTECAN; N [5 (5 TERT BUTYL 2 OXAZOLYLMETHYLTHIO) 2 THIAZOLYL]ISONIPECOTAMIDE; P 276 00; PHA 848125; R 547; ROSCOVITINE; UNCLASSIFIED DRUG; ZK 304709;

ANTINEOPLASTIC ACTIVITY; CANCER CELL; CELL CYCLE; CELL CYCLE ARREST; CELL CYCLE G0 PHASE; CELL CYCLE G1 PHASE; CELL CYCLE G2 PHASE; CELL CYCLE M PHASE; CELL CYCLE REGULATION; CELL CYCLE S PHASE; CELL PROLIFERATION; DRUG EFFICACY; DRUG MECHANISM; ENZYME ACTIVITY; ENZYME INHIBITION; FATIGUE; HEADACHE; HUMAN; HYPOTENSION; MULTIPLE CYCLE TREATMENT; NAUSEA; NEOPLASM; PRIORITY JOURNAL; REVIEW; SIDE EFFECT; SWEATING; VOMITING; XEROSTOMIA;

ANIMALS; ANTINEOPLASTIC AGENTS; CELL CYCLE; CLINICAL TRIALS AS TOPIC; CYCLIN-DEPENDENT KINASE INHIBITOR PROTEINS; HUMANS; MOLECULAR TARGETED THERAPY; NEOPLASMS;

EID: 70450280886     PISSN: 01676997     EISSN: None     Source Type: Journal    
DOI: 10.1007/s10637-009-9236-6     Document Type: Review

References (59)

1. JW Harper PD Adams 2001 Cyclin-dependent kinases Chem Rev 101 8 2511 2526 10.1021/cr0001030 1:CAS:528:DC%2BD3MXkvV2qtL0%3D 11749386 (Pubitemid 35373032)
2. GK Schwartz MA Shah 2005 Targeting the cell cycle: a new approach to cancer therapy J Clin Oncol 23 36 9408 9421 10.1200/JCO.2005.01.5594 1:CAS:528:DC%2BD28Xnt1ymtA%3D%3D 16361640 (Pubitemid 46260200)
3. M Malumbres M Barbacid 2007 Cell cycle kinases in cancer Curr Opin Genet Dev 17 1 60 65 10.1016/j.gde.2006.12.008 1:CAS:528:DC%2BD2sXnslOnsQ%3D%3D 17208431 (Pubitemid 46109297)
4. S Ortega M Malumbres M Barbacid 2002 Cyclin D-dependent kinases, INK4 inhibitors and cancer Biochim Biophys Acta 1602 1 73 87 1:CAS:528: DC%2BD38XktVKgu7o%3D 11960696
5. EA Sausville 2002 Complexities in the development of cyclin-dependent kinase inhibitor drugs Trends Mol Med 8 4)(Suppl S32 S37 10.1016/S1471-4914(02) 02308-0 1:CAS:528:DC%2BD38XitlGhsLg%3D 11927285 (Pubitemid 34297076)
6. Tibes R, Jimeno A, Von Hoff D. Phase I dose escalation study of the oral multi-CDK inihibitor PHA-848125. Proc Am Soc Clin Oncol 2008: abstr 3531.
7. KS Joshi MJ Rathos P Mahajan V Wagh S Shenoy D Bhatia 2007 P276-00, a novel cyclin-dependent inhibitor induces G1-G2 arrest, shows antitumor activity on cisplatin-resistant cells and significant in vivo efficacy in tumor models Mol Cancer Ther 6 3 926 934 10.1158/1535-7163.MCT-06-0614 1:CAS:528: DC%2BD2sXivV2nur4%3D 17363487 (Pubitemid 46554562)
8. Tannock IF, Hill RP, Bristow RG (2005) The Basic Science of Oncology. Mc Graw-Hill Professional, New York
9. Y Geng Q Yu E Sicinska M Das JE Schneider S Bhattacharya 2003 Cyclin E ablation in the mouse Cell 114 4 431 443 10.1016/S0092-8674(03)00645-7 1:CAS:528:DC%2BD3sXmvFahtbo%3D 12941272 (Pubitemid 37100992)
10. HX An MW Beckmann G Reifenberger HG Bender D Niederacher 1999 Gene amplification and overexpression of CDK4 in sporadic breast carcinomas is associated with high tumor cell proliferation Am J Pathol 154 1 113 118 1:CAS:528:DyaK1MXnsFGjsw%3D%3D 9916925
11. F Mendrzyk B Radlwimmer S Joos F Kokocinski A Benner DE Stange 2005 Genomic and protein expression profiling identifies CDK6 as novel independent prognostic marker in medulloblastoma J Clin Oncol 23 34 8853 8862 10.1200/JCO.2005.02.8589 1:CAS:528:DC%2BD28XisFE%3D 16314645 (Pubitemid 46211532)
12. AO Yurakh D Ramos S Calabuig-Farinas JA Lopez-Guerrero J Rubio E Solsona 2006 Molecular and immunohistochemical analysis of the prognostic value of cell-cycle regulators in urothelial neoplasms of the bladder Eur Urol 50 3 506 515 10.1016/j.eururo.2006.03.027 1:CAS:528:DC%2BD28XhtVSrs7%2FM 16624482 (Pubitemid 44189058)
13. O Tetsu F McCormick 2003 Proliferation of cancer cells despite CDK2 inhibition Cancer Cell 3 3 233 245 10.1016/S1535-6108(03)00053-9 1:CAS:528:DC%2BD3sXislOrtb0%3D 12676582 (Pubitemid 37443879)
14. I Collins MD Garrett 2005 Targeting the cell division cycle in cancer: CDK and cell cycle checkpoint kinase inhibitors Curr Opin Pharmacol 5 4 366 373 10.1016/j.coph.2005.04.009 1:CAS:528:DC%2BD2MXlvFKlsL0%3D 15964238 (Pubitemid 40932038)
15. T Oelgeschlager 2002 Regulation of RNA polymerase II activity by CTD phosphorylation and cell cycle control J Cell Physiol 190 2 160 169 10.1002/jcp.10058 1:CAS:528:DC%2BD38Xjt1Crtg%3D%3D 11807820 (Pubitemid 34027819)
16. MV Blagosklonny 2004 Flavopiridol, an inhibitor of transcription: implications, problems and solutions Cell Cycle 3 12 1537 1542 1:CAS:528:DC%2BD28XjtVersb0%3D 15539947
17. BA Carlson MM Dubay EA Sausville L Brizuela PJ Worland 1996 Flavopiridol induces G1 arrest with inhibition of cyclin-dependent kinase (CDK) 2 and CDK4 in human breast carcinoma cells Cancer Res 56 13 2973 2978 1:CAS:528: DyaK28XjvFCktr0%3D 8674031
18. G Melillo EA Sausville K Cloud T Lahusen L Varesio AM Senderowicz 1999 Flavopiridol, a protein kinase inhibitor, down-regulates hypoxic induction of vascular endothelial growth factor expression in human monocytes Cancer Res 59 21 5433 5437 1:CAS:528:DyaK1MXnt1Gjur8%3D 10554012
19. JC Byrd C Shinn JK Waselenko EJ Fuchs TA Lehman PL Nguyen 1998 Flavopiridol induces apoptosis in chronic lymphocytic leukemia cells via activation of caspase-3 without evidence of bcl-2 modulation or dependence on functional p53 Blood 92 10 3804 3816 1:CAS:528:DyaK1cXnsVKlt78%3D 9808574
20. S Kitada JM Zapata M Andreeff JC Reed 2000 Protein kinase inhibitors flavopiridol and 7-hydroxy-staurosporine down-regulate antiapoptosis proteins in B-cell chronic lymphocytic leukemia Blood 96 2 393 397 1:CAS:528: DC%2BD3cXltVGhtL4%3D 10887097
21. AM Senderowicz D Headlee SF Stinson RM Lush N Kalil L Villalba 1998 Phase I trial of continuous infusion flavopiridol, a novel cyclin-dependent kinase inhibitor, in patients with refractory neoplasms J Clin Oncol 16 9 2986 2999 1:CAS:528:DyaK1cXmtFSls7Y%3D 9738567
22. JP Thomas KD Tutsch JF Cleary HH Bailey R Arzoomanian D Alberti 2002 Phase I clinical and pharmacokinetic trial of the cyclin-dependent kinase inhibitor flavopiridol Cancer Chemother Pharmacol 50 6 465 472 10.1007/s00280-002-0527-2 1:CAS:528:DC%2BD38XovFyrtL8%3D 12451473 (Pubitemid 35435525)
23. M Aklilu HL Kindler RC Donehower S Mani EE Vokes 2003 Phase II study of flavopiridol in patients with advanced colorectal cancer Ann Oncol 14 8 1270 1273 10.1093/annonc/mdg343 1:STN:280:DC%2BD3szkvVaqtA%3D%3D 12881391 (Pubitemid 37039054)
24. S Burdette-Radoux RG Tozer RC Lohmann I Quirt DS Ernst W Walsh 2004 Phase II trial of flavopiridol, a cyclin dependent kinase inhibitor, in untreated metastatic malignant melanoma Invest New Drugs 22 3 315 322 10.1023/B:DRUG. 0000026258.02846.1c 1:CAS:528:DC%2BD2cXjsF2isro%3D 15122079 (Pubitemid 39012571)
25. G Liu DR Gandara PN Lara Jr D Raghavan JH Doroshow P Twardowski 2004 A Phase II trial of flavopiridol (NSC #649890) in patients with previously untreated metastatic androgen-independent prostate cancer Clin Cancer Res 10 3 924 928 10.1158/1078-0432.CCR-03-0050 1:CAS:528:DC%2BD2cXhtFCnsL8%3D 14871968 (Pubitemid 38198891)
26. GK Schwartz D Ilson L Saltz E O'Reilly W Tong P Maslak 2001 Phase II study of the cyclin-dependent kinase inhibitor flavopiridol administered to patients with advanced gastric carcinoma J Clin Oncol 19 7 1985 1992 1:CAS:528:DC%2BD3MXjtVyhu74%3D 11283131
27. GI Shapiro JG Supko A Patterson C Lynch J Lucca PF Zacarola 2001 A phase II trial of the cyclin-dependent kinase inhibitor flavopiridol in patients with previously untreated stage IV non-small cell lung cancer Clin Cancer Res 7 6 1590 1599 1:CAS:528:DC%2BD3MXltV2hsro%3D 11410495
28. JC Byrd TS Lin JT Dalton D Wu MA Phelps B Fischer 2007 Flavopiridol administered using a pharmacologically derived schedule is associated with marked clinical efficacy in refractory, genetically high-risk chronic lymphocytic leukemia Blood 109 2 399 404 10.1182/blood-2006-05-020735 1:CAS:528:DC%2BD2sXivVyktbk%3D 17003373 (Pubitemid 46105932)
29. M Motwani C Rizzo F Sirotnak Y She GK Schwartz 2003 Flavopiridol enhances the effect of docetaxel in vitro and in vivo in human gastric cancer cells Mol Cancer Ther 2 6 549 555 1:CAS:528:DC%2BD3sXlslWkt7Y%3D 12813134
30. MA Shah J Kortmansky M Motwani M Drobnjak M Gonen S Yi 2005 A phase I clinical trial of the sequential combination of irinotecan followed by flavopiridol Clin Cancer Res 11 10 3836 3845 10.1158/1078-0432.CCR-04-2651 1:CAS:528:DC%2BD2MXktFyru7s%3D 15897584 (Pubitemid 40685604)
31. MN Fornier D Rathkopf M Shah S Patil E O'Reilly AN Tse 2007 Phase I dose-finding study of weekly docetaxel followed by flavopiridol for patients with advanced solid tumors Clin Cancer Res 13 19 5841 5846 10.1158/1078-0432. CCR-07-1218 1:CAS:528:DC%2BD2sXhtFSntLrF 17908977 (Pubitemid 47583909)
32. Carvajal RD, Shah MA, Tse R. A phase II study of docetaxel followed by flavopiridol in advanced, gemcitabine-refractory pancreatic cancer. Proc Am Soc Clin Oncol abstr 2008:Abstract 15558.
33. KC Bible JL Lensing SA Nelson YK Lee JM Reid MM Ames 2005 Phase 1 trial of flavopiridol combined with cisplatin or carboplatin in patients with advanced malignancies with the assessment of pharmacokinetic and pharmacodynamic end points Clin Cancer Res 11 16 5935 5941 10.1158/1078-0432.CCR-04-2566 1:CAS:528:DC%2BD2MXos1Cisr4%3D 16115936 (Pubitemid 41170323)
34. S George BS Kasimis J Cogswell P Schwarzenberger GI Shapiro P Fidias 2008 Phase I study of flavopiridol in combination with Paclitaxel and Carboplatin in patients with non-small-cell lung cancer Clin Lung Cancer 9 3 160 165 10.3816/CLC.2008.n.024 1:CAS:528:DC%2BD1cXnvVCrtLk%3D 18621626 (Pubitemid 351880855)
35. EC Busby DF Leistritz RT Abraham LM Karnitz JN Sarkaria 2000 The radiosensitizing agent 7-hydroxystaurosporine (UCN-01) inhibits the DNA damage checkpoint kinase hChk1 Cancer Res 60 8 2108 2112 1:CAS:528:DC%2BD3cXivVaksL4%3D 10786669
36. A Monks ED Harris A Vaigro-Wolff CD Hose JW Connelly EA Sausville 2000 UCN-01 enhances the in vitro toxicity of clinical agents in human tumor cell lines Invest New Drugs 18 2 95 107 10.1023/A:1006313611677 1:CAS:528: DC%2BD3cXkt1CntLY%3D 10857990 (Pubitemid 30261284)
37. J Kortmansky MA Shah A Kaubisch A Weyerbacher S Yi W Tong 2005 Phase I trial of the cyclin-dependent kinase inhibitor and protein kinase C inhibitor 7-hydroxystaurosporine in combination with Fluorouracil in patients with advanced solid tumors J Clin Oncol 23 9 1875 1884 10.1200/JCO.2005.03.116 1:CAS:528:DC%2BD2MXjt1Cku74%3D 15699481 (Pubitemid 46211365)
38. EA Sausville SG Arbuck R Messmann D Headlee KS Bauer RM Lush 2001 Phase I trial of 72-hour continuous infusion UCN-01 in patients with refractory neoplasms J Clin Oncol 19 8 2319 2333 1:CAS:528:DC%2BD3MXjsFeqsrs%3D 11304786
39. S Welch HW Hirte MS Carey SJ Hotte MS Tsao S Brown 2007 UCN-01 in combination with topotecan in patients with advanced recurrent ovarian cancer: a study of the Princess Margaret Hospital Phase II consortium Gynecol Oncol 106 2 305 310 10.1016/j.ygyno.2007.02.018 1:CAS:528:DC%2BD2sXot1ygurg%3D 17537491 (Pubitemid 47096653)
40. PN Lara Jr PC Mack T Synold P Frankel J Longmate PH Gumerlock 2005 The cyclin-dependent kinase inhibitor UCN-01 plus cisplatin in advanced solid tumors: a California cancer consortium phase I pharmacokinetic and molecular correlative trial Clin Cancer Res 11 12 4444 4450 10.1158/1078-0432.CCR-04-2602 1:CAS:528:DC%2BD2MXltFeksrY%3D 15958629 (Pubitemid 40825635)
41. L Meijer E Raymond 2003 Roscovitine and other purines as kinase inhibitors. From starfish oocytes to clinical trials Acc Chem Res 36 6 417 425 10.1021/ar0201198 1:CAS:528:DC%2BD3sXhs1Oksro%3D 12809528
42. SR Whittaker MI Walton MD Garrett P Workman 2004 The Cyclin-dependent kinase inhibitor CYC202 (R-roscovitine) inhibits retinoblastoma protein phosphorylation, causes loss of Cyclin D1, and activates the mitogen-activated protein kinase pathway Cancer Res 64 1 262 272 10.1158/0008-5472.CAN-03-0110 1:CAS:528:DC%2BD2cXkslyksg%3D%3D 14729633 (Pubitemid 38114107)
43. DE MacCallum J Melville S Frame K Watt S Anderson A Gianella-Borradori 2005 Seliciclib (CYC202, R-Roscovitine) induces cell death in multiple myeloma cells by inhibition of RNA polymerase II-dependent transcription and down-regulation of Mcl-1 Cancer Res 65 12 5399 5407 10.1158/0008-5472.CAN-05- 0233 1:CAS:528:DC%2BD2MXltFels7w%3D 15958589 (Pubitemid 40827353)
44. N Raje S Kumar T Hideshima A Roccaro K Ishitsuka H Yasui 2005 Seliciclib (CYC202 or R-roscovitine), a small-molecule cyclin-dependent kinase inhibitor, mediates activity via down-regulation of Mcl-1 in multiple myeloma Blood 106 3 1042 1047 10.1182/blood-2005-01-0320 1:CAS:528:DC%2BD2MXntVSmsrk%3D 15827128 (Pubitemid 41076452)
45. C Benson J White J De Bono A O'Donnell F Raynaud C Cruickshank 2007 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 Br J Cancer 96 1 29 37 10.1038/sj.bjc.6603509 1:CAS:528:DC%2BD2sXis1Khug%3D%3D 17179992 (Pubitemid 46094635)
46. K Bettayeb H Sallam Y Ferandin F Popowycz G Fournet M Hassan 2008 N-&-N, a new class of cell death-inducing kinase inhibitors derived from the purine roscovitine Mol Cancer Ther 7 9 2713 2724 10.1158/1535-7163.MCT-08-0080 1:CAS:528:DC%2BD1cXhtFSms7nL 18790752
47. S Ortega I Prieto J Odajima A Martin P Dubus R Sotillo 2003 Cyclin-dependent kinase 2 is essential for meiosis but not for mitotic cell division in mice Nat Genet 35 1 25 31 10.1038/ng1232 1:CAS:528: DC%2BD3sXmslelsrw%3D 12923533 (Pubitemid 37048592)
48. C Muller-Tidow R Metzger K Kugler S Diederichs G Idos M Thomas 2001 Cyclin E is the only cyclin-dependent kinase 2-associated cyclin that predicts metastasis and survival in early stage non-small cell lung cancer Cancer Res 61 2 647 653 1:CAS:528:DC%2BD3MXht1Gmsbg%3D 11212263
49. KK Hunt K Keyomarsi 2005 Cyclin E as a prognostic and predictive marker in breast cancer Semin Cancer Biol 15 4 319 326 10.1016/j.semcancer.2005.04.007 1:CAS:528:DC%2BD2MXmvVKntbo%3D 16043362 (Pubitemid 41058777)
50. EI Heath K Bible RE Martell DC Adelman PM Lorusso 2008 A phase 1 study of SNS-032 (formerly BMS-387032), a potent inhibitor of cyclin-dependent kinases 2, 7 and 9 administered as a single oral dose and weekly infusion in patients with metastatic refractory solid tumors Invest New Drugs 26 1 59 65 10.1007/s10637-007-9090-3 1:CAS:528:DC%2BD1cXlt1aruw%3D%3D 17938863
51. DW Fry PJ Harvey PR Keller WL Elliott M Meade E Trachet 2004 Specific inhibition of cyclin-dependent kinase 4/6 by PD 0332991 and associated antitumor activity in human tumor xenografts Mol Cancer Ther 3 11 1427 1438 1:CAS:528:DC%2BD2cXpslCkt7c%3D 15542782
52. E Menu J Garcia X Huang M Di Liberto PL Toogood I Chen 2008 A novel therapeutic combination using PD 0332991 and bortezomib: study in the 5T33MM myeloma model Cancer Res 68 14 5519 5523 10.1158/0008-5472.CAN-07-6404 1:CAS:528:DC%2BD1cXovVCgur0%3D 18632601
53. KS Joshi MJ Rathos RD Joshi M Sivakumar M Mascarenhas S Kamble 2007 In vitro antitumor properties of a novel cyclin-dependent kinase inhibitor, P276-00 Mol Cancer Ther 6 3 918 925 10.1158/1535-7163.MCT-06-0613 1:CAS:528: DC%2BD2sXivV2ntbc%3D 17363486 (Pubitemid 46554561)
54. Hirte HW, Baetz T, Vidal L, Fleming GF, Sugimoto AK, Morgan RJ, et al. A phase 1 study of the selective cyclin dependent kinase inhibitor P276-00 in patients with advanced refractory neoplasms. Proc Am Soc Clin Oncol 2007:abstr 14117.
55. W DePinto XJ Chu X Yin M Smith K Packman P Goelzer 2006 In vitro and in vivo activity of R547: a potent and selective cyclin-dependent kinase inhibitor currently in phase I clinical trials Mol Cancer Ther 5 11 2644 2658 10.1158/1535-7163.MCT-06-0355 1:CAS:528:DC%2BD28Xht1els7nM 17121911 (Pubitemid 44848991)
56. Diab S, Eckhardt S, Tan A, Frenette G, Gore L, Depinto W, et al. A phase I study of R547, a novel selective inhibitor of cell cycle and transcriptional cyclin dependent kinases (CDKs). Proc Am Soc Clin Oncol 2007:Abstract 3528.
57. DR Camidge D Smethurst J Growcott NC Barrass JR Foster S Febbraro 2007 A first-in-man phase I tolerability and pharmacokinetic study of the cyclin-dependent kinase-inhibitor AZD5438 in healthy male volunteers Cancer Chemother Pharmacol 60 3 391 398 10.1007/s00280-006-0371-x 1:CAS:528: DC%2BD2sXmsVOjsrk%3D 17115157 (Pubitemid 46944578)
58. DR Camidge M Pemberton J Growcott D Amakye D Wilson H Swaisland 2007 A phase I pharmacodynamic study of the effects of the cyclin-dependent kinase-inhibitor AZD5438 on cell cycle markers within the buccal mucosa, plucked scalp hairs and peripheral blood mononucleocytes of healthy male volunteers Cancer Chemother Pharmacol 60 4 479 488 10.1007/s00280-006-0387-2 1:CAS:528:DC%2BD2sXnvFKnsbo%3D 17143601 (Pubitemid 47084256)
59. G Siemeister U Luecking C Wagner K Detjen C Mc Coy K Bosslet 2006 Molecular and pharmacodynamic characteristics of the novel multi-target tumor growth inhibitor ZK 304709 Biomed Pharmacother 60 6 269 272 10.1016/j.biopha. 2006.06.003 1:CAS:528:DC%2BD28XotlWms7Y%3D 16887322 (Pubitemid 44223936)