Mammalian cells are exposed to a wide variety of genotoxic stresses from both endogenous and exogenous sources. Cells typically exhibit cell cycle delays, or checkpoints, in response to acute genotoxic stress. Other types of cellular responses to DNA damage include apoptosis and probably increases in DNA repair levels. These response pathways are altered in cancer cells, by genetic alterations such as overexpression or mutation of oncogenes, or loss of tumor suppressor gene functions. As cancer chemotherapy relies primarily on the selective killing of cancer cells by DNA-damaging agents, genetic alterations affecting cellular stress response pathways may affect the outcome of cancer treatment.