Methods to study cancer therapeutic drugs that target cell cycle checkpoints

Cell cycle checkpoints operating through a network of multiple signaling pathways provide a key mechanism for self-defense of cells against DNA damage caused by various endogenous or environmental stresses. In cancer treatment, checkpoints are activated in response to diverse DNA-damaging agents and radiation, thus representing a critical barrier limiting therapeutic efficacy. To date, despite efforts to target other components of checkpoint signaling pathways (e.g., ATM, Chk2, Wee1), checkpoint kinase 1 (Chk1) remains the most important target for cancer treatment because of its functional association with essentially all cell cycle checkpoints. The primary goal in the development of therapeutic agents targeting cell cycle checkpoints continues to be improving the anti-cancer activity of chemo- and radiotherapy by abrogating checkpoints necessary for DNA repair, thereby killing cancer cells through engagement of the apoptotic machinery.