Editorial: Cancer-Associated Defects in the DNA Damage Response: Drivers for Malignant Transformation and Potential Therapeutic Targets.

Abstract

Transformation of normal cells into cancer cells almost invariably goes along with increased levels of DNA damage. An important source of DNA damage is the enhanced activity of growth-promoting transcription factors, such as MYC. Oncogenic activation of these transcription factors aberrantly stimulates DNA replication, which leads to replication stress and ensuing DNA breaks. Cells respond to this type of stress by activation of the DNA damage response (DDR). The DDR is a complex signaling network, displaying multiple levels of cross-talk and feed-back control. Its kinase-driven signaling axes ensure rapid responses to DNA lesions, which is complemented by its transcriptional axis that warrants maintained signaling. Ultimately, activation of the DDR prevents further proliferation and thus provides time to repair genotoxic lesions, and in case of excessive levels of DNA damage promotes permanent cell cycle exit (senescence) or programmed cell death (apoptosis). Activation of the DDR thus prevents the outgrowth of incipient tumor cells, early during tumorigenesis.