Title: Flavopiridol, the First Cyclin-Dependent Kinase Inhibitor: Recent Advances in Combination Chemotherapy
Volume: 10
Issue: 11
Author(s): L.-M. Wang and D.-M. Ren
Affiliation:
Keywords:
Anticancer, cancer, CDKIs, combination therapy, flavopiridol, flavonoid, Cyclin-Dependent Kinase Inhibitor, Combination Chemotherapy, Chemotherapeutic agents, Anti-tumor effects, Therapeutic agents, Mammalian enzyme systems, Dysoxylum binectariferum, Vascular endothelial growth factor (VEGF), Inhibit angiogenesis, Structure-activity relationships, Dose-limiting toxicities (DLT), Rohitukine, Oxoflavopiridols, P-TEFb, Adenine binding pocket, Pan-CDK inhibitors, Antiproliferative effect, Antiangiogenic effect, Flavopiridol's activation, Radiation-induced cytotoxicity, Docetaxel (FD), Histone Deacetylase Inhibitors (HDACIs), Cancer cell line OCA-I, Proteasome Inhibitors, Monoclonal Antibodies, Breast cancer mortality, T-cell leukemia, Gemcitabine, non-hematological malignancies, Antineoplastic agents, Gelatin microspheres (GMSs), Hyponatremia, thrombocytopenia, Neutropenia, Mitoxantrone, Humanized anti-Tac antibody, Histone deacetylase inhibitors, Hypoxia-inducible factor
Abstract: The cell cycle is the series of events necessary for the division and duplication of a cell. The dysregulation of the cell cycle can promote the development of cancer. A group of proteins, cyclin-dependent kinases (CDKs), that control the cell cycle, provide new targets for treating cancer. As a result, cyclin-dependent kinase inhibitors (CDKIs) represent a novel class of chemotherapeutic agents. Of these, flavopiridol, a semisynthetic flavonoidal alkaloid, emerged as the first CDKI to enter clinical trials. Preclinical data indicate that flavopiridol could block the proliferation of neoplastic cells and induce programmed cell death as a single agent. Furthermore, recent emerging data revealed that flavopiridol can potentiate, generally in a dose- and sequence-dependent manner, the anti-tumor effects of many established chemotherapeutic agents. This review is primarily focused on the role of flavopiridol in combination with various therapeutic agents that are in or near clinical development.
