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.