Exploiting Replicative Stress to Treat Cancer

Overview

Journal Nat Rev Drug Discov

Specialty Pharmacology

Date 2015 May 9

PMID 25953507

Citations 163

Authors

Matthias Dobbelstein

Claus Storgaard Sorensen

Affiliations

Soon will be listed here.

Abstract

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.

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