New combination therapies with cell-cycle agents.
Cancer cells have deregulated cell-cycle progression with overexpression of positive regulators and inhibition of negative regulators, giving them unlimited replication potential. Therefore, development of agents targeting the deregulated cell cycle has been considered as an ideal strategy for cancer therapy. Cell-cycle-based agents have been categorized as cyclin-dependent kinase inhibitors, Cdc25 inhibitors, checkpoint inhibitors and mitotic inhibitors. These drugs have demonstrated preclinical efficacy, but their efficacy in the clinic has been modest and has been hampered by various side effects. Alternatively, their combination with chemotherapeutic drugs has been studied in different preclinical and clinical settings. Initial reports from these combination studies have been encouraging and suggest that combined drugs may be useful in lowering cancer burden.
Deep
Gagan
G
University of Colorado Denver, School of Pharmacy, Department of Pharmaceutical Sciences, East 4200 9th Street, Box C238, Denver, CO 80262, USA.
Agarwal
Rajesh
R
D000818:Animals; D050256:Antimitotic Agents; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects*; D002986:Clinical Trials as Topic; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology*
D050256:Antimitotic Agents; D004791:Enzyme Inhibitors; D018844:Cyclin-Dependent Kinases