Cyclin-dependent kinases as new targets for the prevention and treatment of cancer

Hematol Oncol Clin North Am. 2002 Oct;16(5):1229-53. doi: 10.1016/s0889-8588(02)00049-7.

Abstract

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.

Publication types

  • Review

MeSH terms

  • Alkaloids / pharmacology
  • Alkaloids / therapeutic use
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Apoptosis / drug effects
  • Cell Cycle / drug effects
  • Cell Differentiation / drug effects
  • Clinical Trials, Phase I as Topic
  • Cyclin-Dependent Kinases / antagonists & inhibitors*
  • Cyclin-Dependent Kinases / physiology
  • Drug Design
  • Drug Screening Assays, Antitumor
  • Enzyme Inhibitors / pharmacology*
  • Enzyme Inhibitors / therapeutic use
  • Flavonoids / pharmacology
  • Flavonoids / therapeutic use
  • Humans
  • Neoplasm Proteins / antagonists & inhibitors*
  • Neoplasm Proteins / physiology
  • Neoplasms / drug therapy*
  • Neoplasms / enzymology
  • Piperidines / pharmacology
  • Piperidines / therapeutic use
  • Signal Transduction / drug effects
  • Staurosporine / analogs & derivatives
  • Transcription, Genetic / drug effects

Substances

  • Alkaloids
  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Flavonoids
  • Neoplasm Proteins
  • Piperidines
  • alvocidib
  • 7-hydroxystaurosporine
  • Cyclin-Dependent Kinases
  • Staurosporine