Potential biomarkers of DNA replication stress in cancer
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Potential biomarkers of DNA replication stress in cancer. / Ren, Liqun; Chen, Long; Wu, Wei; Garribba, Lorenza; Tian, Huanna; Liu, Zihui; Ivan, Vogel; Li, Chunhui; Hickson, Ian D; Liu, Ying.
In: OncoTarget, Vol. 8, No. 23, 2017, p. 36996-37008.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Potential biomarkers of DNA replication stress in cancer
AU - Ren, Liqun
AU - Chen, Long
AU - Wu, Wei
AU - Garribba, Lorenza
AU - Tian, Huanna
AU - Liu, Zihui
AU - Ivan, Vogel
AU - Li, Chunhui
AU - Hickson, Ian D
AU - Liu, Ying
PY - 2017
Y1 - 2017
N2 - Oncogene activation is an established driver of tumorigenesis. An apparently inevitable consequence of oncogene activation is the generation of DNA replication stress (RS), a feature common to most cancer cells. RS, in turn, is a causal factor in the development of chromosome instability (CIN), a near universal feature of solid tumors. It is likely that CIN and RS are mutually reinforcing drivers that not only accelerate tumorigenesis, but also permit cancer cells to adapt to diverse and hostile environments. This article reviews the genetic changes present in cancer cells that influence oncogene-induced RS and CIN, with a particular emphasis on regions of the human genome that show enhanced sensitivity to the destabilizing effects of RS, such as common fragile sites. Because RS exists in a wide range of cancer types, we propose that the proteins involved counteracting this stress are potential biomarkers for indicating the degree of RS in cancer specimens. To test this hypothesis, we conducted a pilot study to validate whether some of proteins that are known from in vitro studies to play an essential role in the RS pathway could be suitable as a biomarker. Our results indicated that this is possible. With this review and pilot study, we aim to accelerate the development of a biomarker for analysis of RS in tumor biopsy specimens, which could ultimately help to stratify patients for different forms of therapy such as the RS inhibitors already undergoing clinical trials.
AB - Oncogene activation is an established driver of tumorigenesis. An apparently inevitable consequence of oncogene activation is the generation of DNA replication stress (RS), a feature common to most cancer cells. RS, in turn, is a causal factor in the development of chromosome instability (CIN), a near universal feature of solid tumors. It is likely that CIN and RS are mutually reinforcing drivers that not only accelerate tumorigenesis, but also permit cancer cells to adapt to diverse and hostile environments. This article reviews the genetic changes present in cancer cells that influence oncogene-induced RS and CIN, with a particular emphasis on regions of the human genome that show enhanced sensitivity to the destabilizing effects of RS, such as common fragile sites. Because RS exists in a wide range of cancer types, we propose that the proteins involved counteracting this stress are potential biomarkers for indicating the degree of RS in cancer specimens. To test this hypothesis, we conducted a pilot study to validate whether some of proteins that are known from in vitro studies to play an essential role in the RS pathway could be suitable as a biomarker. Our results indicated that this is possible. With this review and pilot study, we aim to accelerate the development of a biomarker for analysis of RS in tumor biopsy specimens, which could ultimately help to stratify patients for different forms of therapy such as the RS inhibitors already undergoing clinical trials.
U2 - 10.18632/oncotarget.16940
DO - 10.18632/oncotarget.16940
M3 - Journal article
C2 - 28445142
VL - 8
SP - 36996
EP - 37008
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
IS - 23
ER -
ID: 177185787