Seliciclib in malignancies

Expert Opinion on Investigational Drugs

Volumn 18, Issue 12, 2009, Pages 1957-1965

  Aldoss, Ibrahim T ^a   Tashi, Tsewang ^a   Ganti, Apar Kishor ^b,c  

^a CREIGHTON UNIVERSITY MEDICAL CENTER   (United States)

^b VA NEBRASKA WESTERN IOWA HEALTH CARE SYSTEM   (United States)

^c UNIVERSITY OF NEBRASKA MEDICAL CENTER   (United States)

Author keywords

Cancer; Cell cycle; Cyclin dependent kinase inhibitor; Roscovitine; Seliciclib

Indexed keywords

ALEMTUZUMAB; BOHEMINE; BORTEZOMIB; CISPLATIN; CYCLIN DEPENDENT KINASE 7; CYCLIN DEPENDENT KINASE 9; CYCLIN DEPENDENT KINASE INHIBITOR; DOCETAXEL; DOXORUBICIN; GEMCITABINE; OLOMUCINE; PLACEBO; PROTEIN P53; ROSCOVITINE; TRASTUZUMAB; UNCLASSIFIED DRUG;

ADVANCED CANCER; ANOREXIA; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; AREA UNDER THE CURVE; ASTHENIA; CANCER OF UNKNOWN PRIMARY SITE; CLINICAL TRIAL; COLORECTAL CANCER; CONTROLLED CLINICAL TRIAL; CREATININE BLOOD LEVEL; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG DISTRIBUTION; DRUG DOSE ESCALATION; DRUG DOSE INCREASE; DRUG DOSE REGIMEN; DRUG EFFICACY; DRUG ERUPTION; DRUG EXCRETION; DRUG HALF LIFE; DRUG MECHANISM; DRUG METABOLISM; DRUG POTENTIATION; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; FATIGUE; FOOD DRUG INTERACTION; HUMAN; HYPERGLYCEMIA; HYPOKALEMIA; HYPONATREMIA; KIDNEY TUBULE DISORDER; LETHARGY; LIVER FUNCTION; LUNG CANCER; LUNG NON SMALL CELL CANCER; MALIGNANT NEOPLASTIC DISEASE; MAXIMUM PLASMA CONCENTRATION; MAXIMUM TOLERATED DOSE; MULTIPLE CYCLE TREATMENT; NASOPHARYNX CARCINOMA; NAUSEA; OPTIMAL DRUG DOSE; OVARY CANCER; PROGRESSION FREE SURVIVAL; PROSTATE CANCER; RANDOMIZED CONTROLLED TRIAL; RECOMMENDED DRUG DOSE; REVIEW; SIDE EFFECT; TIME TO MAXIMUM PLASMA CONCENTRATION; TREATMENT RESPONSE; UTERINE CERVIX CANCER; VOMITING;

ANTINEOPLASTIC AGENTS; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; CLINICAL TRIALS AS TOPIC; CYCLIN-DEPENDENT KINASES; DRUG SCREENING ASSAYS, ANTITUMOR; ENZYME INHIBITORS; HUMANS; MODELS, BIOLOGICAL; NEOPLASMS; PURINES;

EID: 72249094390     PISSN: 13543784     EISSN: None     Source Type: Journal    
DOI: 10.1517/13543780903418445     Document Type: Review

References (74)

1. Sherr CJ. Cancer cell cycles. Science 1996;274:1672-1677
2. Sherr CJ. The Pezcoller lecture: cancer cell cycles revisited. Cancer Res 2000;60:3689-3695
3. Morgan DO. Principles of CDK regulation. Nature 1995;374:131-134
4. Grana X, Reddy EP. Cell cycle control in mammalian cells: role of cyclins, cyclin dependent kinases (CDKs), growth suppressor genes and cyclin-dependent kinase inhibitors (CKIs). Oncogene 1995;11:211-219
5. Malumbres M, Barbacid M. Mammalian cyclin-dependent kinases. Trends Biochem Sci 2005;30:630-641
6. Malumbres M, Barbacid M. Cell cycle, CDKs and cancer: a changing paradigm. Nat Rev Cancer 2009;9:153-166
7. Sherr CJ. G1 phase progression: cycling on cue. Cell 1994;79:551-555
8. Harper JW, Adams PD. Cyclin-dependent kinases. Chem Rev 2001;101:2511-2526
9. Oelgeschlager T. Regulation of RNA polymerase II activity by CTD phosphorylation and cell cycle control. J Cell Physiol 2002;190:160-169
10. An HX, Beckmann MW, Reifenberger G, et al. Gene amplification and overexpression of CDK4 in sporadic breast carcinomas is associated with high tumor cell proliferation. Am J Pathol 1999;154:113-118
11. Mendrzyk F, Radlwimmer B, Joos S, et al. Genomic and protein expression profiling identifies CDK6 as novel independent prognostic marker in medulloblastoma. J Clin Oncol 2005;23:8853-62
12. Yurakh AO, Ramos D, Calabuig-Farinas S, et al. Molecular and immunohistochemical analysis of the prognostic value of cell-cycle regulators in urothelial neoplasms of the bladder. Eur Urol 2006;50:506-15; discussion 515 1
13. Ortega S, Malumbres M, Barbacid M. Cyclin D-dependent kinases, INK4 inhibitors and cancer. Biochim Biophys Acta 2002;1602:73-87
14. Arnold A, Papanikolaou A. Cyclin D1 in breast cancer pathogenesis. J Clin Oncol 2005;23:4215-4224
15. Bergsagel PL, Kuehl WM, Zhan F, et al. Cyclin D dysregulation: an early and unifying pathogenic event in multiple myeloma. Blood 2005;106:296-303
16. Senderowicz AM. Novel small molecule cyclin-dependent kinases modulators in human clinical trials. Cancer Biol Ther 2003;2:S84-95
17. Bartkova J, Lukas J, Guldberg P, et al. The p16-cyclin D/Cdk4-pRb pathway as a functional unit frequently altered in melanoma pathogenesis. Cancer Res 1996;56:5475-5483
18. Bartkova J, Lukas J, Muller H, et al. Abnormal patterns of D-type cyclin expression and G1 regulation in human head and neck cancer. Cancer Res 1995;55:949-956
19. Aagaard L, Lukas J, Bartkova J, et al. Aberrations of p16Ink4 and retinoblastoma tumour-suppressor genes occur in distinct sub-sets of human cancer cell lines. Int J Cancer 1995;61:115-120
20. Lukas J, Aagaard L, Strauss M, Bartek J. Oncogenic aberrations of p16INK4/ CDKN2 and cyclin D1 cooperate to deregulate G1 control. Cancer Res 1995;55:4818-4823
21. Malumbres M, Barbacid M. To cycle or not to cycle: a critical decision in cancer. Nat Rev Cancer 2001;1:222-231
22. Chen YN, Sharma SK, Ramsey TM, et al. Selective killing of transformed cells by cyclin/cyclin-dependent kinase 2 antagonists. Proc Natl Acad Sci USA 1999;96:4325-4329
23. Chen W, Lee J, Cho SY, Fine HA. Proteasome-mediated destruction of the cyclin a/cyclin-dependent kinase 2 complex suppresses tumor cell growth in vitro and in vivo. Cancer Res 2004;64:3949-3957
24. Mendoza N, Fong S, Marsters J, et al. Selective cyclin-dependent kinase 2/ cyclin A antagonists that differ from ATP site inhibitors block tumor growth. Cancer Res 2003;63:1020-1024
25. Shapiro GI. Cyclin-dependent kinase pathways as targets for cancer treatment. J Clin Oncol 2006;24:1770-83
26. O'Connor DS, Wall NR, Porter AC, Altieri DC. A p34(cdc2) survival checkpoint in cancer. Cancer Cell 2002;2:43-54
27. Rieder CL, Maiato H. Stuck in division or passing through: what happens when cells cannot satisfy the spindle assembly checkpoint. Dev Cell 2004;7:637-651
28. Weaver BA, Cleveland DW. Decoding the links between mitosis, cancer, and chemotherapy: the mitotic checkpoint, adaptation, and cell death. Cancer Cell 2005;8:7-12
29. Wesierska-Gadek J, Borza A, Walzi E, et al. Outcome of treatment of human HeLa cervical cancer cells with roscovitine strongly depends on the dosage and cell cycle status prior to the treatment. J Cell Biochem 2009;106:937-955
30. Yu C, Krystal G, Dent P, Grant S. Flavopiridol potentiates STI571-induced mitochondrial damage and apoptosis in BCR-ABL-positive human leukemia cells. Clin Cancer Res 2002;8:2976-2984
31. Vesely J, Havlicek L, Strnad M, et al. Inhibition of cyclin-dependent kinases by purine analogues. Eur J Biochem 1994;224:771-786
32. Legraverend M, Ludwig O, Bisagni E, et al. Synthesis of C2 alkynylated purines, a new family of potent inhibitors of cyclin-dependent kinases. Bioorg Med Chem Lett 1998;8:793-8
33. Legraverend M, Ludwig O, Bisagni E, et al. Synthesis and in vitro evaluation of novel 2,6,9-trisubstituted purines acting as cyclin-dependent kinase inhibitors. Bioorg Med Chem 1999;7:1281-1293 (Pubitemid 29292370)
34. Wang S, McClue SJ, Ferguson JR, et al. Synthesis and configuration of the cyclin-dependent kinase inhibitor roscovitine and its enantiomer. Tetrahedron Asymmetry 2001;12:2891-2894
35. Vita M, Abdel-Rehim M, Nilsson C, et al. Stability, pKa and plasma protein binding of roscovitine. J Chromatogr B Analyt Technol Biomed Life Sci 2005;821:75-80
36. Meijer L, Raymond E. Roscovitine and other purines as kinase inhibitors. From starfish oocytes to clinical trials. Acc Chem Res 2003;36:417-425
37. Bettayeb K, Oumata N, Echalier A, et al. CR8, a potent and selective, roscovitine-derived inhibitor of cyclin-dependent kinases. Oncogene 2008;27:5797-5807
38. Lacrima K, Rinaldi A, Vignati S, et al. Cyclin-dependent kinase inhibitor seliciclib shows in vitro activity in diffuse large B-cell lymphomas. Leuk Lymphoma 2007;48:158-167
39. Ribas J, Boix J, Meijer L. (R)-roscovitine (CYC202, Seliciclib) sensitizes SH-SY5Y neuroblastoma cells to nutlin-3-induced apoptosis. Exp Cell Res 2006;312:2394-2400
40. Goh BC, Peh BK, Cui CY, et al. Seliciclib (R-roscovitine) induces apoptosis in undifferentiated nasopharyngeal cancer (NPC) in vivo and in vitro. J Clin Oncol (Meeting Abstracts) 2005;23:3145
41. McClue SJ, Blake D, Clarke R, et al. In vitro and in vivo antitumor properties of the cyclin dependent kinase inhibitor CYC202 (R-roscovitine). Int J Cancer 2002;102:463-468
42. Meijer L, Borgne A, Mulner O, et al. Biochemical and cellular effects of roscovitine, a potent and selective inhibitor of the cyclin-dependent kinases cdc2, cdk2 and cdk Eur J Biochem 1997;243:527-536
43. MacCallum DE, Melville J, Frame S, et al. 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 2005;65:5399-5407
44. Raje N, Kumar S, Hideshima T, et al. Seliciclib (CYC202 or R-roscovitine), a small-molecule cyclin-dependent kinase inhibitor, mediates activity via down-regulation of Mcl-1 in multiple myeloma. Blood 2005;106:1042-1047
45. Whittaker SR, Walton MI, Garrett MD, Workman P. 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 2004;64:262-272
46. Alvi AJ, Austen B, Weston VJ, et al. A novel CDK inhibitor, CYC202 (R-roscovitine), overcomes the defect in p53-dependent apoptosis in B-CLL by down-regulation of genes involved in transcription regulation and survival. Blood 2005;105:4484-4491
47. Hahntow IN, Schneller F, Oelsner M, et al. Cyclin-dependent kinase inhibitor Roscovitine induces apoptosis in chronic lymphocytic leukemia cells. Leukemia 2004;18:747-755
48. Kim EH, Kim SU, Shin DY, Choi KS. Roscovitine sensitizes glioma cells to TRAIL-mediated apoptosis by downregulation of survivin and XIAP. Oncogene 2004;23:446-456
49. Raynaud FI, Whittaker SR, Fischer PM, et al. In vitro and in vivo pharmacokinetic-pharmacodynamic relationships for the trisubstituted aminopurine cyclin-dependent kinase inhibitors olomoucine, bohemine and CYC20 2. Clin Cancer Res 2005;11:4875-4887
50. Weingrill E, Wolfler A, Strunk D, et al. Roscovitine in B-chronic lymphocytic leukemia cells: high apoptosis-inducing efficacy and synergism with alemtuzumab independent of the patients' pretreatment status. Haematologica 2007;92:1286-1288
51. Lacrima K, Valentini A, Lambertini C, et al. In vitro activity of cyclin-dependent kinase inhibitor CYC202 (Seliciclib, R-roscovitine) in mantle cell lymphomas. Ann Oncol 2005;16:1169-1176
52. Galimberti F, Thompson S, Liu X, et al. Targeting the cyclin E-Cdk-2 complex represses lung cancer growth by triggering apoptosis and anaphase catastrophe. Proc Am Assoc Cancer Res 2009:4784
53. Fleming IN, Hogben M, Frame S, et al. Synergistic inhibition of ErbB signaling by combined treatment with seliciclib and ErbB-targeting agents. Clin Cancer Res 2008;14:4326-4335
54. Mgbonyebi OP, Russo J, Russo IH. Roscovitine inhibits the proliferative activity of immortal and neoplastic human breast epithelial cells. Anticancer Res 1998;18:751-755
55. Mgbonyebi OP, Russo J, Russo IH. Roscovitine induces cell death and morphological changes indicative of apoptosis in MDA-MB-231 breast cancer cells. Cancer Res 1999;59:1903-10
56. Ortiz-Ferron G, Yerbes R, Eramo A, et al. Roscovitine sensitizes breast cancer cells to TRAIL-induced apoptosis through a pleiotropic mechanism. Cell Res 2008;18:664-676
57. Appleyard MV, O'Neill MA, Murray KE, et al. Seliciclib (CYC202, R-roscovitine) enhances the antitumor effect of doxorubicin in vivo in a breast cancer xenograft model. Int J Cancer 2009;124:465-72
58. Wesierska-Gadek J, Wandl S, Kramer MP, et al. Roscovitine up-regulates p53 protein and induces apoptosis in human HeLaS(3) cervix carcinoma cells. J Cell Biochem 2008;105:1161-1171
59. Coley HM, Shotton CF, Kokkinos MI, Thomas H. The effects of the CDK inhibitor seliciclib alone or in combination with cisplatin in human uterine sarcoma cell lines. Gynecol Oncol 2007;105:462-9
60. de la Motte S, Gianella-Borradori A. Pharmacokinetic model of R-roscovitine and its metabolite in healthy male subjects. Int J Clin Pharmacol Ther 2004;42:232-239
61. Benson C, White J, De Bono J, et al. 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 2007;96:29-37
62. Hsieh WS, Soo R, Peh BK, et al. Pharmacodynamic effects of seliciclib, an orally administered cell cycle modulator, in undifferentiated nasopharyngeal cancer. Clin Cancer Res 2009;15:1435-1442
63. Nutley BP, Raynaud FI, Wilson SC, et al. Metabolism and pharmacokinetics of the cyclin-dependent kinase inhibitor R-roscovitine in the mouse. Mol Cancer Ther 2005;4:125-139
64. Vita M, Abdel-Rehim M, Olofsson S, et al. Tissue distribution, pharmacokinetics and identification of roscovitine metabolites in rat. Eur J Pharm Sci 2005;25:91-103
65. Pierga J-Y, Faivre S, Vera K, et al. A phase I and pharmacokinetic (PK) trial of CYC202, a novel oral cyclin-dependent kinase (CDK) inhibitor, in patients (pts) with advanced solid tumors. Proc Am Soc Clin Oncol 2003;22:840
66. Jackson RC, Barnett AL, McClue SJ, Green SR. Seliciclib, a cell-cycle modulator that acts through the inhibition of cyclin-dependent kinases. Expert Opin Drug Discov 2008;3:131-43 Available from: http://www.cyclacel.com/cyc/rd/ programs/oncology/seliciclib/seliciclib.pdf
67. Siegel-Lakhai WS, Rodenstein DO, Beijnen JH, et al. Phase I study of seliciclib (CYC202 or R-roscovitine) in combination with gemcitabine (gem)/ cisplatin (cis) in patients with advanced non-small cell lung cancer (NSCLC). J Clin Oncol (Meeting Abstracts) 2005;23:2060 Available from: http:// clinicaltrials.gov/ show/NCT00372073
68. Yeo W, Goh B, Le Tourneau C, et al. A phase II randomized study of oral seliciclib in patients with previously treated nasopharyngeal carcinoma. J Clin Oncol (Meeting Abstracts) 2009;27:6026
69. Yu Q, Geng Y, Sicinski P. Specific protection against breast cancers by cyclin D1 ablation. Nature 2001;411:1017-1021
70. Grant S, Roberts JD. The use of cyclin-dependent kinase inhibitors alone or in combination with established cytotoxic drugs in cancer chemotherapy. Drug Resist Updat 2003;6:15-26
71. Shah MA, Schwartz GK. Cell cycle-mediated drug resistance: an emerging concept in cancer therapy. Clin Cancer Res 2001;7:2168-2181
72. Motwani M, Delohery TM, Schwartz GK. Sequential dependent enhancement of caspase activation and apoptosis by flavopiridol on paclitaxel-treated human gastric and breast cancer cells. Clin Cancer Res 1999;5:1876-1883
73. Wang S, Guo CY, Castillo A, et al. Effect of bryostatin 1 on taxol-induced apoptosis and cytotoxicity in human leukemia cells (U937). Biochem Pharmacol 1998;56:635-644
74. Wang S, Wang Z, Boise LH, et al. Bryostatin 1 enhances paclitaxel-induced mitochondrial dysfunction and apoptosis in human leukemia cells (U937) ectopically expressing Bcl-xL. Leukemia 1999;13:1564-1573 (Pubitemid 29465619)