The DNA damage response in tumorigenesis and cancer treatment

Jiri Bartek and Jiri Lukas

The DNA damage response pathways can activate cell cycle checkpoints (which can involve p53) to arrest the cell either transiently or permanently (senescence) or they can activate specific DNA repair pathways in response to certain types of DNA damage. Some of the proteins in these pathways are mutated or non-functional in human tumours. This can cause cancer cells to be more reliant on an intact DNA repair pathway or survival, providing a therapeutic window. Inhibition of these intact pathways can selectively target tumour cells and the success of this strategy is illustrated by the progress of poly(ADP-ribose) polymerase (PARP) inhibitors in early phase clinical trials. This Poster highlights how the DNA damage response is thought to protect against tumour progression and the therapeutic rationale for specifically targeting members of the DNA damage response pathways. Some of the drugs that are under development or in clinical trials are also included.

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