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Development of cell-cycle inhibitors for cancer therapy

By M.A. Dickson and G.K. Schwartz

Abstract

The cell cycle governs the transition from quiescence through cell growth to proliferation. The key parts of the cell cycle machinery are the cyclin-dependent kinases (cdks) and the regulatory proteins called cyclins. The cdks are rational targets for cancer therapy because their expression in cancer cells is often aberrant and their inhibition can induce cell death. Inhibitors of cdks can also block transcription

Topics: Drug Development in Contemporary Oncology
Publisher: Multimed Inc.
OAI identifier: oai:pubmedcentral.nih.gov:2669234
Provided by: PubMed Central
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    1. A doseescalation study of indisulam in combination with capecitabine (Xeloda) in patients with solid tumours.
    2. (2007). A first-in-man phase i tolerability and pharmacokinetic study of the cyclindependent kinase-inhibitor AZD5438 in healthy male volunteers. Cancer Chemother Pharmacol
    3. A multi-center phase ii study of sequential paclitaxel and bryostatin-1 (NSC 339555) in patients with untreated, advanced gastric or gastroesophageal junction adenocarcinoma.
    4. (2005). A novel c d k inhibitor, CYC202 (R-roscovitine), overcomes the defect in p53-dependent apoptosis in b-c l l by down-regulation of genes involved in transcription regulation and survival. Blood
    5. A novel liposomal formulation of flavopiridol.
    6. A p34 c d c 2 survival checkpoint in cancer.
    7. 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.
    8. A phase i and pharmacokinetic study of indisulam in combination with carboplatin.
    9. A phase i clinical trial of the sequential combination of irinotecan followed by flavopiridol.
    10. (2009). A phase i dose escalation trial of a daily oral c d k 4/6 inhibitor PD-0332991 [abstract 3550].
    11. (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
    12. A phase i study of flavopiridol and docetaxel.
    13. (1995). A phase i trial of bryostatin 1 in patients with advanced malignancy using a 24 hour intravenous infusion.
    14. 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.
    15. A phase ii evaluation of flavopiridol as second-line chemotherapy of endometrial carcinoma: a Gynecologic Oncology Group study.
    16. A randomized phase ii pharmacokinetic and pharmacodynamic study of indisulam as second-line therapy in patients with advanced non-small cell lung cancer.
    17. A restriction point for control of normal animal cell proliferation.
    18. An a t m -independent S-phase checkpoint response involves c h k 1 pathway.
    19. (2003). Antitumour activity of CYC202, a cyclin-dependent kinase inhibitor, in human tumor xenografts in vitro [abstract 713]. Amer Assoc Cancer Res
    20. b i r inging chromosomes through cell division—and survivin’ the experience. Cell 2000;102:545–8.
    21. c d k inhibitors: positive and negative regulators of G1-phase progression. Genes Dev 1999;13:1501–12.
    22. (1999). Cancer and the cell cycle.
    23. (1994). Cell cycle control and cancer.
    24. (1995). Cell cycle control in mammalian cells: role of cyclins, cyclin dependent kinases (c d k s), growth suppressor genes and cyclin-dependent kinase inhibitors (c k i s). Oncogene
    25. checkpoints after ionizing irradiation.
    26. Clinical response and pharmacokinetics from a phase i study of an active dosing schedule of flavopiridol in relapsed chronic lymphocytic leukemia.
    27. (1994). Cyclin A/c d k 2 binds directly to E2F-1 and inhibits the d n a -binding activity of E2F-1/DP-1 by phosphorylation.
    28. Cyclin D1 and mammary carcinoma: new insights from transgenic mouse models.
    29. (2004). Cyclin-dependent kinase inhibitor roscovitine induces apoptosis in chronic lymphocytic leukemia cells. Leukemia
    30. Cyclins and cell cycle checkpoints. Annu Rev Pharmacol Toxicol 1999;39:295–312.
    31. (2001). d n a methylation: an alternative pathway to cancer. Ann Surg
    32. Differential regulation of E2F transactivation by cyclin/c d k 2 complexes.
    33. Discovery of a potent and selective inhibitor of cyclin-dependent kinase 4/6.
    34. Drosophila Aurora A kinase is required to localize d-t a c c to centrosomes and to regulate astral microtubules.
    35. (1996). Elledge SJ. c d k inhibitors in development and cancer. Curr Opin Genet Dev
    36. (1993). Expression and amplification of cyclin genes in human breast cancer. Oncogene
    37. Flavopiridol administered using a pharmacologically derived schedule is associated with marked clinical efficacy in refractory, genetically high-risk chronic lymphocytic leukemia.
    38. (2008). Flavopiridol displays preclinical activity in acute lymphoblastic leukemia. Pediatr Blood Cancer
    39. Flavopiridol in patients with relapsed or refractory multiple myeloma: a phase 2 trial with clinical and pharmacodynamic end-points.
    40. (1997). How cells get the right chromosomes.
    41. (1998). Human and yeast c d k -activating kinases (c a k s) display distinct substrate specificities.
    42. In vitro and in vivo antitumour properties of the cyclin dependent kinase inhibitor CYC202 (R-roscovitine).
    43. (1995). Inhibition of leukemic cell growth by the protein kinase C activator bryostatin 1 correlates with the dephosphorylation of cyclin-dependent kinase 2. Cancer Res
    44. Mantle cell lymphoma cells express predominantly cyclin D1a isoform and are highly sensitive to selective inhibition of c d k 4 kinase activity.
    45. (1995). Mutations in Aurora prevent centrosome separation leading to the formation of monopolar spindles.
    46. (1994). Negative regulation of the growth-promoting transcription factor E2F-1 by a stably bound cyclin A–dependent protein kinase.
    47. (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
    48. Phase i clinical and pharmacokinetic study of E7070, a novel sulfonamide given as a 5-day continuous infusion repeated every 3 weeks in patients
    49. (2007). Phase i dose-finding study of weekly docetaxel followed by flavopiridol for patients with advanced solid tumors. Clin Cancer Res
    50. (2006). Phase i study of bryostatin 1 and fludarabine in patients with chronic lymphocytic leukemia and indolent (non-Hodgkin’s) lymphoma. Clin Cancer Res
    51. Phase i study of bryostatin 1 and gemcitabine.
    52. (2008). Phase i study of flavopiridol in combination with paclitaxel and carboplatin in patients with non-small-cell lung cancer. Clin Lung Cancer
    53. (2005). Phase ii study of E7070 in patients with metastatic melanoma. Ann Oncol
    54. Phase ii trial of flavopiridol, a cyclin dependent kinase inhibitor, in untreated metastatic malignant melanoma.
    55. (2008). Phase ii trial of sequential paclitaxel and 1 h infusion of bryostatin-1 in patients with advanced esophageal cancer. Cancer Chemother Pharmacol
    56. (1995). Phosphorylation of E2F-1 by cyclin A–c d k 2. Oncogene
    57. Polar expeditions—provisioning the centrosome for mitosis.
    58. Pyrido[2,3-d]pyrimidin-7-ones as specific inhibitors of cyclin-dependent kinase 4.
    59. Regulation of r n a polymerase ii activity by c t d phosphorylation and cell cycle control.
    60. Regulation of transcription elongation by phosphorylation.
    61. (2004). Roscovitine sensitizes glioma cells to t r a i l -mediated apoptosis by downregulation of survivin and x i a p . Oncogene
    62. (1999). Selective killing of transformed cells by cyclin/cyclin-dependent kinase 2 antagonists.
    63. (2005). Seliciclib (CYC202, R-roscovitine) induces cell death in multiple myeloma cells by inhibition of r n a polymerase ii–dependent transcription and down-regulation of Mcl-1. Cancer Res
    64. Sequential flavopiridol, cytosine arabinoside, and mitoxantrone: a phase ii trial in adults with poor-risk acute myelogenous leukemia.
    65. (2004). Specific inhibition of cyclin-dependent kinase 4/6 by PD 0332991 and associated antitumour activity in human tumor xenografts. Mol Cancer Ther
    66. (2000). Spindle assembly and the art of regulating microtubule dynamics by m a p s and Stathmin/Op18. Trends Cell Biol
    67. (2002). Studies on the mechanism of action of CYC202 (R-roscovitine) [abstract 666]. Amer Assoc Cancer Res
    68. The a t m -Chk2-c d c 25A checkpoint pathway guards against radioresistant d n a synthesis.
    69. (2008). The cyclindependent kinase inhibitor flavopiridol potentiates the effects of topoisomerase i poisons by suppressing Rad51 expression in a p53-dependent manner. Cancer Res
    70. The d n a damage response: putting checkpoints in perspective.
    71. (2001). The molecular basis and potential role of survivin in cancer diagnosis and therapy. Trends Mol Med
    72. The Pezcoller Lecture: cancer cell cycles revisited.
    73. (1998). The role of protein stability in the cell cycle and cancer. Biochim Biophys Acta
    74. (1998). The S phase: beginning, middle, and end: a perspective.
    75. (1996). The spindle assembly checkpoint.
    76. To cycle or not to cycle: a critical decision in cancer.
    77. Transcription inhibition by flavopiridol: mechanism of chronic lymphocytic leukemia cell death.

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