Exploiting replicative stress to treat cancer

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


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Cell Cycle Checkpoints / drug effects
  • Cell Cycle Checkpoints / genetics
  • DNA Damage / drug effects
  • DNA Damage / genetics
  • DNA Replication / drug effects
  • DNA Replication / genetics*
  • Drug Delivery Systems / methods
  • Humans
  • Neoplasms / drug therapy*
  • Neoplasms / genetics*
  • Treatment Outcome


  • Antineoplastic Agents