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 Citationer (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.

Originalsprog	Engelsk
Tidsskrift	Nature Reviews. Drug Discovery
Vol/bind	14
Udgave nummer	6
Sider (fra-til)	405-23
Antal sider	19
ISSN	1474-1776
DOI	https://doi.org/10.1038/nrd4553
Status	Udgivet - 3 jun. 2015

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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.",

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

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AU - Sørensen, Claus Storgaard

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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.

KW - Animals

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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DO - 10.1038/nrd4553

M3 - Review

C2 - 25953507

SN - 1474-1776

VL - 14

SP - 405

EP - 423

JO - Nature Reviews Drug Discovery

JF - Nature Reviews Drug Discovery

IS - 6

ER -

Exploiting replicative stress to treat cancer

Abstract

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