This Article Full Text Full Text (PDF) eLetters: Submit a response to this article Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services E-mail this article link to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints/Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Senderowicz, A. M. Search for Related Content PubMed PubMed Citation Articles by Senderowicz, A. M.

The Cell Cycle as a Target for Cancer Therapy: Basic and Clinical Findings with the Small Molecule Inhibitors Flavopiridol and UCN-01

Molecular Therapeutics Unit, Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, USA

Correspondence: Adrian M. Senderowicz, M.D., National Institutes of Health, Oral and Pharyngeal Cancer Branch, NIDCR Building 30; Room 211, 30 Convent Drive, Bethesda, Maryland 20892-4340, USA. Telephone: 301-594-5270; Fax: 301-402-0823; e-mail: asenderowicz{at}dir.nidcr.nih.gov

Many tumor types are associated with genetic changes in the retinoblastoma pathway, leading to hyperactivation of cyclin-dependent kinases and incorrect progression through the cell cycle. Small-molecule cyclin-dependent kinase inhibitors are being developed as therapeutic agents. Of these, flavopiridol and UCN-01 are being explored in cancer patients in phase I and phase II clinical trials, both as single agents and in combination with conventional chemotherapeutic agents. The present article discusses the mechanisms of action of flavopiridol and UCN-01 as well as the outcome of clinical trials with these novel agents.

Key Words. Cell cycle • Cyclin-dependent kinases • Flavopiridol • UCN-01 • Phase I trials • Clinical trials

This article has been cited by other articles:

				Y. Takada, G. Sethi, B. Sung, and B. B. Aggarwal Flavopiridol Suppresses Tumor Necrosis Factor-Induced Activation of Activator Protein-1, c-Jun N-Terminal Kinase, p38 Mitogen-Activated Protein Kinase (MAPK), p44/p42 MAPK, and Akt, Inhibits Expression of Antiapoptotic Gene Products, and Enhances Apoptosis through Cytochrome c Release and Caspase Activation in Human Myeloid Cells Mol. Pharmacol., May 1, 2008; 73(5): 1549 - 1557. [Abstract] [Full Text] [PDF]

				C. Richard, D. Matthews, W. Duivenvoorden, J. Yau, P. S. Wright, and J. P.H. Th'ng Flavopiridol Sensitivity of Cancer Cells Isolated from Ascites and Pleural Fluids Clin. Cancer Res., May 1, 2005; 11(9): 3523 - 3529. [Abstract] [Full Text] [PDF]

				H.-P. Lin, S. K. Kulp, P.-H. Tseng, Y.-T. Yang, C.-C. Yang, C.-S. Chen, and C.-S. Chen Growth inhibitory effects of celecoxib in human umbilical vein endothelial cells are mediated through G1 arrest via multiple signaling mechanisms Mol. Cancer Ther., December 1, 2004; 3(12): 1671 - 1680. [Abstract] [Full Text] [PDF]

				P. Stanhope-Baker, P. M. Kessler, W. Li, M. L. Agarwal, and B. R. G. Williams The Wilms Tumor Suppressor-1 Target Gene Podocalyxin Is Transcriptionally Repressed by p53 J. Biol. Chem., August 6, 2004; 279(32): 33575 - 33585. [Abstract] [Full Text] [PDF]

				Y. Dai, X.-Y. Pei, M. Rahmani, D. H. Conrad, P. Dent, and S. Grant Interruption of the NF-{kappa}B pathway by Bay 11-7082 promotes UCN-01-mediated mitochondrial dysfunction and apoptosis in human multiple myeloma cells Blood, April 1, 2004; 103(7): 2761 - 2770. [Abstract] [Full Text] [PDF]

				A. Boitano, J. A. Ellman, G. D. Glick, and A. W. Opipari Jr. The Proapoptotic Benzodiazepine Bz-423 Affects the Growth and Survival of Malignant B Cells Cancer Res., October 15, 2003; 63(20): 6870 - 6876. [Abstract] [Full Text] [PDF]

				X. Hong, L. Lei, and R. Glas Tumors Acquire Inhibitor of Apoptosis Protein (IAP)-mediated Apoptosis Resistance through Altered Specificity of Cytosolic Proteolysis J. Exp. Med., June 16, 2003; 197(12): 1731 - 1743. [Abstract] [Full Text] [PDF]

				A. F.W. Frijhoff, C. J. Conti, and A. M. Senderowicz Second Symposium of Novel Molecular Targets for Cancer Therapy Oncologist, August 1, 2002; 7(90003): 1 - 3. [Full Text] [PDF]