Cell cycle target validation: approaches and successes

Evasion of the checks and balances that govern the human cell division cycle lies at the heart of all proliferative diseases. Because of the astonishing variety of ways that cancer cells manage to achieve growth advantages over normally proliferating cells, it can be expected that pharmacological reinstatement of cell cycle progression control should also be achievable in a multitude of ways. Very few cell cycle targets have so far been exploited for the discovery of mechanism-based anticancer drugs; even fewer targets have yielded actual or experimental clinical drugs. Here, we discuss the approaches that have been and are beginning to be used to identify and validate molecular targets whose pharmacological modulation holds the promise of nongenotoxic and inherently selective cancer therapy. We discuss an approach based on using the genetically amenable organism Drosophila melanogaster as a model for the identification of cell cycle targets, particularly those involved in the processes of mitosis.