Journal
EXPERIMENTAL CELL RESEARCH
Volume 329, Issue 1, Pages 26-34Publisher
ELSEVIER INC
DOI: 10.1016/j.yexcr.2014.09.019
Keywords
Replication Stress; ATR; CHK1; Cancer
Categories
Funding
- Spanish Ministry of Science [SAF2011-23753]
- Association for International Cancer Research [12-0229]
- Fundacio LaMarato de TV3 [33/C (2013)]
- Howard Hughes Medical Institute
- European Research Council [ERC-210520]
- Worldwide Cancer Research [12-0229] Funding Source: researchfish
Ask authors/readers for more resources
Problems arising during DNA replication require the activation of the ATR-CHK1 pathway to ensure the stabilization and repair of the forks, and to prevent the entry into mitosis with unreplicated genomes. Whereas the pathway is essential at the cellular level, limiting its activity is particularly detrimental for some cancer cells. Here we review the links between replication stress (RS) and cancer, which provide a rationale for the use of ATR and Chk1 inhibitors in chemotherapy. First, we describe how the activation of oncogene-induced RS promotes genome rearrangements and chromosome instability, both of which could potentially fuel carcinogenesis. Next, we review the various pathways that contribute to the suppression of RS, and how mutations in these components lead to increased cancer incidence and/or accelerated ageing. Finally, we summarize the evidence showing that tumors with high levels of RS are dependent on a proficient RS-response, and therefore vulnerable to ATR or Chk1 inhibitors. (C) 2014 Elsevier Inc. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available