Cyclin-dependent kinases as new targets for the prevention and treatment of cancer.
Based on the frequent aberration in cell cycle regulatory pathways in human cancer by cdk hyperactivation, novel ATP competitive cdk inhibitors are being developed. The first two tested in clinical trials, flavopiridol and UCN-01, showed promising results with evidence of antitumor activity and plasma concentrations sufficient to inhibit cdk-related functions. Best schedule to be administered, combination with standard chemotherapeutic agents, best tumor types to be targeted, and demonstration of cdk modulation from tumor samples from patients in these trials are important questions that need to be answered to advance these agents to the clinic.
Senderowicz
Adrian M
AM
Molecular Therapeutics Unit, Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Building 30, Room 211, Bethesda, MD 20892-4340, USA. adrian.senderowicz@nih.gov
D000470:Alkaloids / Q000494:pharmacology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D017321:Clinical Trials, Phase I as Topic; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors* / Q000502:physiology; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D005419:Flavonoids / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000502:physiology; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D010880:Piperidines / Q000494:pharmacology / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects; D019311:Staurosporine / Q000031:analogs & derivatives; D014158:Transcription, Genetic / Q000187:drug effects
D000470:Alkaloids; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D005419:Flavonoids; D009363:Neoplasm Proteins; D010880:Piperidines; C077990:alvocidib; C054852:7-hydroxystaurosporine; D018844:Cyclin-Dependent Kinases; D019311:Staurosporine