The impact of impaired DNA damage responses on cells, tissues and organisms

Current cancer therapies rely mainly on DNA damaging insults (irradiation, DNA alkylating agents, DNA synthesis inhibitors etc.). The rationale behind these treatments is that rapidly growing cancer cells suffer more from DNA damaging insults. Unfortunately, the majority of current therapies fail to attack tumor cells specifically and hence normal cells are also being damaged. In order to improve cancer therapy, it will be of key value to increase the sensitivity of tumor cells to DNA damage or decrease DNA damage sensitivity in the surrounding normal tissue. In order to reach this goal, DNA damage responses in their broadest sense need to be educidated in detail. The latter is not an easy task because DNA damage responses are not only insult-specific but also vary among various cell types and tissues which is attributed to differences in metabolic state, genetic background and nerve or hormone regulation.