Preclinical and clinical development of the cyclin-dependent kinase inhibitor flavopiridol

Clinical Cancer Research

Volumn 10, Issue 12 II, 2004, Pages

  Shapiro, Geoffrey I ^a,b  

^a DANA FARBER CANCER INSTITUTE   (United States)

^b BRIGHAM AND WOMEN S HOSPITAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTINEOPLASTIC AGENT; CARBOPLATIN; CYCLIN A; CYCLIN B; CYCLIN D1; CYCLIN DEPENDENT KINASE 1; CYCLIN DEPENDENT KINASE 2; CYCLIN DEPENDENT KINASE INHIBITOR; DOCETAXEL; FLAVOPIRIDOL; GEMCITABINE; PACLITAXEL; TAXANE DERIVATIVE; TRANSCRIPTION FACTOR E2F1;

APOPTOSIS; CANCER CELL CULTURE; CANCER CHEMOTHERAPY; CELL CYCLE; CLINICAL TRIAL; CONFERENCE PAPER; CONTINUOUS INFUSION; GROWTH INHIBITION; HUMAN; HUMAN CELL; LUNG CANCER; LUNG NON SMALL CELL CANCER; NEUTROPENIA; PHARMACODYNAMICS; PHASE 1 CLINICAL TRIAL; PHASE 2 CLINICAL TRIAL; PRIORITY JOURNAL; TREATMENT OUTCOME; TUMOR GROWTH;

ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; APOPTOSIS; CELL CYCLE; CLINICAL TRIALS; CYCLIN-DEPENDENT KINASES; DRUG ADMINISTRATION SCHEDULE; FLAVONOIDS; HUMANS; NEOPLASMS; PIPERIDINES; TUMOR CELLS, CULTURED;

EID: 3042536038     PISSN: 10780432     EISSN: None     Source Type: Journal    
DOI: 10.1158/1078-0432.CCR-040020     Document Type: Conference Paper

References (60)

1. Meyerson M, Enders GH, Wu CL, et al. A family of human cdc2-related protein kinases. EMBO J 1992;11:2909-17.
2. 1 phase progression: cycling on cue. Cell 1994;79:551-5.
3. Pines J. Cyclins: wheels within wheels. Cell Growth Differ 1991;2:305-10.
4. 1 cyclin-dependent kinases. Genes Dev 1995;9:1149-63.
5. 1-phase progression. Genes Dev 1999;13:1501-12.
6. Sherr CJ. Cancer cell cycles. Science (Wash DC) 1996;274:1672-7.
7. Hall M, Peters G. Genetic alterations of cyclins, cyclin-dependent kinases, and cdk inhibitors in human cancer. Adv Cancer Res 1996;68:67-108.
8. Shapiro GI, Harper JW. Anticancer drug targets: cell cycle and checkpoint control. J Clin Investig 1999;104:1645-53.
9. Senderowicz AM, Sausville EA. Preclinical and clinical development of cyclin-dependent kinase modulators. J Natl Cancer Inst (Bethesda) 2000;92:376-87.
10. Mani S, Wang C, Wu K, Francis R, Pestell R. Cyclin-dependent kinase inhibitors: novel anticancer agents. Exp Opin Investig Drugs 2000;9:1849-70.
11. Shapiro GI. Small molecule inhibitors of cyclin-dependent kinases. In: Blagosklonny M, editor. Cell cycle checkpoints and cancer. Georgetown, TX: Landes Bioscience; 2001. p, 208-34.
12. Geng Y, Yu Q, Sicinska E, et al. Cyclin E ablation in the mouse. Cell 2003;114:431-43.
13. Tetsu O, McCormick F. Proliferation of cancer cells despite cdk2 inhibition. Cancer Cell 2003;3:233-45.
14. Ortega S, Prieto I, Odajima J, et al. Cyclin-dependent kinase 2 is essential for meiosis but not for mitotic cell division in mice. Nat Genet 2003;35:25-31.
15. Sausville EA. Complexities in the development of cyclin-dependent kinase inhibitor drugs. Trends Mol Med 2002;8:S32-7.
16. Sedlacek HH, Czech J, Naik R, et al. Flavopiridol (L86 8275; NSC 649890), a new kinase inhibitor for tumor therapy. Int J Oncol 1996;9:1143-68.
17. Losiewicz MD, Carlson BA, Kaur G, Sausville EA, Worland PJ. Potent inhibition of cdc2 kinase activity by the flavonoid L86-8275. Biochem Biophys Res Commun 1994;201:589-95.
18. Carlson BA, Pearlstein RA, Naik RG, et al. Inhibition of CDK2, CDK4 and CDK7 by flavopiridol and structural analogs. Proc Am Assoc Cancer Res 1996;37:424.
19. 1 arrest with inhibition of cyclin-dependent kinase (CDK)2 and CDK4 in human breast carcinoma cells. Cancer Res 1996;56:2973-8.
20. De Azevedo WF, Mueller-Dieckmann HJM, Schulze-Gahmen U, et al. Structural basis for specificity and potency of a flavonoid inhibitor of human CDK2, a cell cycle kinase. Proc Natl Acad Sci USA 1996;93:2735-40.
21. Worland P, Kaur G, Stetler-Stevenson M, et al. Alteration of the phosphorylation state of p34cdc2 kinase by the flavone L86-8275 in breast carcinoma cells. Biochem Pharmacol 1993;46:1831-40.
22. Chao SH, Fujinaga K, Marion JE, et al. Flavopiridol inhibits P-TEFb and btocks HIV-1 replication. J Biol Chem 2000;275:28345-8.
23. Chao SH, Price DH. Flavopiridol inactivates p-TEFb and blocks most RNA polymerase II transcription in vivo. J Biol Chem 2001;276:31793-9.
24. Lam LT, Pickeral OK, Peng AC, et al. Genomic-scale measurement of mRNA turnover and the mechanisms of action of the anti-cancer drug flavopiridol. Genome Biol 2001;2:0041.1-11.
25. Carlson B, Lahusen T, Singh S, et al. Down-regulation of cyclin D1 by transcriptional repression in MCF-7 human breast carcinoma cells induced by flavopiridol. Cancer Res 1999;59:4634-41.
26. Sedlacek HH. Mechanisms of action of flavopiridol. Crit Rev Oncol Hematol 2001;38:139-70.
27. Bible KC, Kaufmann SH. Flavopiridol: a cytotoxic flavone that induces cell death in noncycling A549 human lung carcinoma cells. Cancer Res 1996;56:4856-61.
28. Shapiro GI, Koestner DA, Matranga CB, Rollins BJ. Flavopiridol induces cell cycle arrest and p53-independent apoptosis in non-small cell lung cancer cell lines. Clin Cancer Res 1999;5:2925-38.
29. Shapiro GI, Supko JG, Patterson A, et al. A Phase 1I trial of the cyclin-dependent kinase inhibitor flavopiridol in patients with previously untreated stage IV non-small cell lung cancer. Clin Cancer Res 2001;7:1500-9.
30. Matranga CB, Shapiro GI. Selective sensitization of transformed cells to flavopiridol-induced apoptosis following recruitment to S-phase. Cancer Res 2002;62:1707-17.
31. Bible KC, Kaufmann SH. Cytotoxic synergy between flavopiridol and various antineoplastic agents: the importance of sequence of administration. Cancer Res 1997;57:3375-80.
32. Jung CP, Motwani MV, Schwartz GK. Flavopiridol increases sensitization to gemcitabine in human gastrointestinal cancer cell lines and correlates with down-regulation of the ribonucleotide reductase M2 subunit. Clin Cancer Res 2001;7:2527-36.
33. Krek W, Ewen ME, Shirodkar S, et al. Negative regulation of the growth-promoting transcription factor E2F-1 by a stably bound cyclin A-dependent protein kinase. Cell 1994;78:161-72.
34. Dynlacht BD, Flores O, Lees JA, Harlow E. Differential regulation of E2F transactivation by cyclin-cdk2 complexes. Genes Dev 1994;8:1772-86.
35. Xu M, Sheppard KA, Peng CY, Yee AS, Piwinica-Worms H. Cyclin A/Cdk2 binds directly to E2F-1 and inhibits the DNA-binding activity of E2F-1/DP-1 by phosphorylation. Mol Cell Biol 1994;14:8420-31.
36. Kitagawa M, Higashi H, Suzuki-Takahashi I, et al. Phosphorylation of E2F-1 by cyclin A-cdk2. Oncogene 1995;10:229-36.
37. Peeper DS, Keblusek P, Helin K, et al. Phosphorylation of a specific cdk site in E2F-1 affects its electrophoretic mobility and promotes pRB-binding in vitro. Oncogene 1995;10:39-48.
38. Vandel L, Kouzarides T. Residues phosphorylated by TFIIH are required for E2F-1 degradation during S-phase. EMBO J 1999;18:4280-91.
39. Krek W, Xu G, Livingston DM. Cyclin A-kinase regulation of E2F-1 DNA binding function underlies suppression of an S phase checkpoint. Cell 1995;83:1149-58.
40. Chen YNP, Sharma SK, Ramsey TM, et al. Selective killing of transformed cells by cyclin/cyclin-dependent kinase 2 antagonists. Proc Natl Acad Sci USA 1999;96:4325-9.
41. Ma Y, Cress D, Haura EB. Flavopiridol-induced apoptosis is mediated through up-regulation of E2F-1 and repression of Mcl-1. Mol Cancer Ther 2003;2:73-81.
42. Jiang J, Matranga CB, Cai D, et al. Flavopiridol-induced apoptosis during S phase requires E2F-1 and inhibition of cyclin A-dependent kinase activity. Cancer Res 2003;63:7410-22.
43. Goffin J, Appleman L, Ryan D, et al. A Phase I trial of gemcitabine followed by flavopiridol in patients with solid tumors. Lung Cancer 2003;41:S179.
44. 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;5:1876-83.
45. O'Connor DS, Wall NR, Porter ACG, Altieri DC. A p34cdc2 survival checkpoint in cancer. Cancer Cell 2002;2:43-54.
46. 34 by flavopiridol enhances tumor cell apoptosis. Cancer Res 2003;63:230-5.
47. Schwartz GK, O'Reilly E, Ilson D, et al. Phase I study of the cyclin-dependent kinase inhibitor flavopiridol in combination with paclitaxel in patients with advanced solid tumors. J Clin Oncol 2002;20:2157-70.
48. Gries JM, Kasimis B, Schwarzenberger P, et al. Phase I study of HMR1275 (flavopiridol) in non-small cell lung cancer (NSCLC) patients after 24 hr IV administration in combination with paclitaxel and carboplatin. Proc Am Soc Clin Oncol 2002;21:94a.
49. Kasimis B, Rocha-Lima C, Cogswell J, et al. Phase I study evaluating 1-hr flavopiridol (HMR 1275) in combination with docetaxel in previously treated non-small cell lung cancer (NSCLC) patients. Proc Am Soc Clin Oncol 2003;22:669.
50. Bissery MC, Lejeune P, Vignaud P. The combination of flavopiridol with docetaxel is synergistic in a murine adenocarcinoma model MA13/C. Proc Am Soc Clin Oncol 2002;21:117a.
51. Motwani M, Rizzo C, Sirotnak F, She Y, Schwartz GK. Flavopiridol enhances the effect of docetaxel in vitro and in vivo in human gastric cancer cells. Mol Cancer Ther 2003;2:549-55.
52. Senderowicz AM, Headlee D, Stinson SF, et al. Phase I trial of continuous infusion flavopiridol, a novel cyclin-dependent kinase inhibitor, in patients with refractory neoplasms. J Clin Oncol 1998;16:2986-99.
53. Thomas JP, Tutsch KD, Cleary JF, et al. Phase I clinical and pharmacokinetic trial of the cyclin-dependent kinase inhibitor flavopiridol. Cancer Chemother Pharmacol 2002;50:465-72.
54. Stadler WM, Vogelzang NJ, Amato R, et al. Flavopiridol, a novel cyclin-dependent kinase inhibitor, in metastatic renal cancer: a University of Chicago Phase II consortium study. J Clin Oncol 2000;18:371-5.
55. Arguello F, Alexander M, Sterry JA, et al. Flavopiridol induces apoptosis of normal lymphoid cells, causes immunosuppression and has potent antitumor activity in vivo against human leukemia and lymphoma xenografts. Blood 1998;91:2482-90.
56. Patel V, Senderowicz AM, Pinto JD, et al. Flavopiridol, a novel cyclin-dependent kinase inhibitor, suppresses the growth of head and neck squamous cell carcinomas by inducing apoptosis. J Clin Investig 1998;102:1674-81.
57. Zhai S, Figg WD, Headlee D, et al. Pharmacokinetics (PK) of flavopiridol IV bolus in patients with refractory neoplasms. Clin Cancer Res 2000;6(Suppl):4529s.
58. Tan AR, Headlee D, Messmann R, et al. Phase I clinical and pharmacokinetic study of flavopiridol administered as a daily 1-hour infusion in patients with advanced neoplasms. J Clin Oncol 2002;20:4074-82.
59. 1/S cyclin-dependent kinases. J Biol Chem 1997;272:12738-46.
60. 18F]FLT uptake by positron emission tomography with Ki-67 immunohistochemistry and flow cytometry in lung tumors. Clin Cancer Res 2002;8:3315-23.