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RAD51 as a potential surrogate marker for DNA repair capacity in solid malignancies
M. Gachechiladze, J. Škarda, A. Soltermann, M. Joerger,
Language English Country United States
Document type Journal Article, Review
PubMed
28477336
DOI
10.1002/ijc.30764
Knihovny.cz E-resources
- MeSH
- Drug Resistance, Neoplasm genetics MeSH
- DNA, Neoplasm drug effects radiation effects MeSH
- Genes, BRCA1 MeSH
- Genes, BRCA2 MeSH
- Precision Medicine MeSH
- Humans MeSH
- Biomarkers, Tumor genetics metabolism MeSH
- Neoplasms drug therapy genetics metabolism radiotherapy MeSH
- DNA Repair genetics MeSH
- Poly(ADP-ribose) Polymerase Inhibitors therapeutic use MeSH
- Polymorphism, Genetic MeSH
- Cell Proliferation genetics MeSH
- Recombinational DNA Repair genetics MeSH
- Rad51 Recombinase genetics metabolism MeSH
- Radiation Tolerance genetics MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
Targeting deficient mechanisms of cellular DNA repair still represents the basis for the treatment of the majority of solid tumors, and increased DNA repair capacity is a hallmark mechanism of resistance not only to DNA-damaging treatments such as cytotoxic drugs and radiotherapy, but also to small molecule targeted drugs such as inhibitors of poly-ADP ribose polymerase (PARP). Hence, there is substantial medical need for potent and convenient biomarkers of individual response to DNA-targeted treatment in personalized cancer care. RAD51 is a highly conserved protein that catalyzes DNA repair via homologous recombination, a major DNA repair pathway which directly modulates cellular sensitivity to DNA-damaging treatments. The clinical and biological significance of RAD51 protein expression is still under investigation. Pre-clinical studies consistently show the important role of nuclear RAD51 immunoreactivity in chemo- and radioresistance. Validating data from clinical trials however is limited at present, and some clinical studies show controversial results. This review gives a comprehensive overview on the current knowledge about the prognostic and predictive value of RAD51 protein expression and genetic variability in patients with solid malignancies.
Department of Medical Oncology and Hematology Cantonal Hospital St Gallen Switzerland
Department of Pathology and Molecular Pathology University Hospital Zurich Switzerland
References provided by Crossref.org
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