Targeting the Cell Cycle to Kill Cancer Cells

Tumors are actively dividing tissues and this renders them susceptible to drugs and treatments that cause DNA damage in specific phases of the cell cycle. Spindle-targeting drugs invoke a cellular response whose normal function is to ensure that each daughter cell receives a copy of each chromosome at division. This response normally delays the cell cycle, however the anti-spindle drugs cause a prolonged cell cycle block that ultimately leads to cell death. Movement of cells from one phase of the cell cycle to the next is controlled by the Cyclin-dependent kinases (CDKs). There are currently 12 known CDKs, although many of these enzymes are not involved in cell cycle regulation. Cell cycle checkpoints originally were defined as pathways that ensure that cell cycle events occur only when previous cell cycle processes are completed successfully. The orderly progression through mitosis relies on multiple cell cycle specific kinases, which are good targets for the development of small molecular inhibitors. Several of these kinases have received attention as potential targets of novel chemotherapeutics.