Potential biomarkers of DNA replication stress in cancer
Autor: | Wei Wu, Chunhui Li, Zihui Liu, Liqun Ren, Lorenza Garribba, Long Chen, Ying Liu, Ian D. Hickson, Huanna Tian, Ivan Vogel |
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Jazyk: | angličtina |
Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
DNA Replication replication stress Carcinogenesis Pilot Projects MiDAS Biology medicine.disease_cause Chromosome Section cancer biomarker 03 medical and health sciences 0302 clinical medicine Chromosome instability Chromosomal Instability Neoplasms medicine Biomarkers Tumor Humans Genetics Mutation Genome Human Chromosomal fragile site Cancer medicine.disease Biomarker (cell) Research Paper: Chromosome 030104 developmental biology Oncology 030220 oncology & carcinogenesis Cancer cell Cancer research Human genome chromosome instability common fragile sites |
Zdroj: | Oncotarget Ren, L, Chen, L, Wu, W, Garribba, L, Tian, H, Liu, Z, Ivan, V, Li, C, Hickson, I D & Liu, Y 2017, ' Potential biomarkers of DNA replication stress in cancer ', OncoTarget, vol. 8, no. 23, pp. 36996-37008 . https://doi.org/10.18632/oncotarget.16940 |
ISSN: | 1949-2553 |
Popis: | 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. |
Databáze: | OpenAIRE |
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