Breaking the DNA damage response via serine/threonine kinase inhibitors to improve cancer treatment.

Breaking the DNA damage response via serine/threonine kinase inhibitors to improve cancer treatment. Curr Med Chem. 2018 Jan 16;: Authors: Rozpedek W, Pytel D, Nowak-Zdunczyk A, Lewko D, Wojtczak R, Diehl JA, Majsterek I Abstract Multiple, both endogenous and exogenous, sources may induce DNA damage and DNA replication stress. Cells have developed DNA damage response (DDR) signaling pathways to maintain genomic stability and effectively detect and repair DNA lesions. Serine/threonine kinases such as Ataxia-telangiectasia mutated (ATM) and Ataxia-telangiectasia and Rad3-Related (ATR) are the major regulators of DDR, since after sensing stalled DNA replication forks, DNA double- or single-strand breaks, may directly phosphorylate and activate their downstream targets, that play a key role in DNA repair, cell cycle arrest and apoptotic cell death. Interestingly, key components of DDR signaling networks may constitute an attractive targets for anti-cancer therapy through two distinct potential approaches: as a chemo- and radiosensitizers to enhance the effectiveness of currently used genotoxic treatment or as a single agents to exploit defects in DDR in cancer cells via synthetic lethal approach. Moreover, the newest data reported that serine/threonine protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) is also closely associated with cancer development and progression. Thereby, utilization of small-molecule, serine/threonine...
Source: Current Medicinal Chemistry - Category: Chemistry Authors: Tags: Curr Med Chem Source Type: research