Exploiting replicative stress to treat cancer

Matthias Dobbelstein; Claus Storgaard Sørensen

doi:10.1038/nrd4553

Exploiting replicative stress to treat cancer

Matthias Dobbelstein, Claus Storgaard Sørensen

157 Citations (Scopus)

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.

Original language	English
Journal	Nature Reviews. Drug Discovery
Volume	14
Issue number	6
Pages (from-to)	405-23
Number of pages	19
ISSN	1474-1776
DOIs	https://doi.org/10.1038/nrd4553
Publication status	Published - 3 Jun 2015

Keywords

Animals
Antineoplastic Agents
Cell Cycle Checkpoints
DNA Damage
DNA Replication
Drug Delivery Systems
Humans
Neoplasms
Treatment Outcome

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/nrd4553

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title = "Exploiting replicative stress to treat cancer",

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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N2 - 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.

AB - 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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KW - Antineoplastic Agents

KW - Cell Cycle Checkpoints

KW - DNA Damage

KW - DNA Replication

KW - Drug Delivery Systems

KW - Humans

KW - Neoplasms

KW - Treatment Outcome

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JO - Nature Reviews Drug Discovery

JF - Nature Reviews Drug Discovery

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ER -

Exploiting replicative stress to treat cancer

Abstract

Keywords

UN SDGs

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