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Nat Rev Drug Discov. 2015 Jun;14(6):405-23. doi: 10.1038/nrd4553. Epub 2015 May 8.

Exploiting replicative stress to treat cancer.

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Institute of Molecular Oncology, Göttingen Center of Molecular Biosciences, Ernst Caspari Haus, University of Göttingen, 37077 Göttingen, Germany.
Biotech Research and Innovation Centre, University of Copenhagen, 2200 Copenhagen, Denmark.


DNA replication in cancer cells is accompanied by stalling and collapse of the replication fork and signalling in response to DNA damage and/or premature mitosis; these processes are collectively known as 'replicative stress'. Progress is being made to increase our understanding of the mechanisms that govern replicative stress, thus providing ample opportunities to enhance replicative stress for therapeutic purposes. Rather than trying to halt cell cycle progression, cancer therapeutics could aim to increase replicative stress by further loosening the checkpoints that remain available to cancer cells and ultimately inducing the catastrophic failure of proliferative machineries. In this Review, we outline current and future approaches to achieve this, emphasizing the combination of conventional chemotherapy with targeted approaches.

[Indexed for MEDLINE]

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