Review of flavopiridol, a cyclin-dependent kinase inhibitor, as breast cancer therapy.
Disrupting the cell cycle through the inhibition of cyclin-dependent kinases (CDKs) is an important therapeutic strategy in the treatment of cancer. Flavopiridol is the first CDK inhibitor to be tested in clinical trials. It has been shown to cause cell cycle arrest, induce apoptosis, inhibit angiogenesis, and potentiate the effects of chemotherapy. In this review, the rationale for using a CDK inhibitor as therapy for breast cancer is described and the preclinical studies performed with flavopiridol in breast cancer cell lines are highlighted. Flavopiridol is currently undergoing phase II testing as monotherapy and phase I and/or II evaluation in combination with traditional chemotherapy agents. The assessment of CDK inhibition as evidence of flavopiridol's targeted effect in serial biopsies of tumor and surrogate tissues is also under investigation in these protocols. The interruption of the cell cycle through modulation of CDKs with an agent such as flavopiridol has potential therapeutic efficacy, especially in combination with chemotherapy.
Cancer Therapeutics Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD20889, USA.
Antoinette R
AR
Tan
Sandra M
SM
Swain
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D015415:Biomarkers; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors* / Q000502:physiology; D005260:Female; D005419:Flavonoids / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D010880:Piperidines / Q000494:pharmacology / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D015415:Biomarkers; D005419:Flavonoids; D010880:Piperidines; C077990:alvocidib; D018844:Cyclin-Dependent Kinases