Journal
INTERNATIONAL JOURNAL OF CANCER
Volume 141, Issue 7, Pages 1286-1294Publisher
WILEY
DOI: 10.1002/ijc.30764
Keywords
RAD51; prognosis; BRCAness; chemotherapy; radiotherapy
Categories
Funding
- Ministry of Education Czech republic-MSMT [61875921, NPS I LO1304, RVO: 61989592]
- Ministry of Health Czech republic (IGA MZ CR) [10259-3, 9959-3, RVO: FNOL00098892]
- Palacky University [91110281]
- Swiss Cancer League [F-8770131-01]
- Swiss National Science Foundation SystemsX [M-8770401-02]
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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 DNAtargeted 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.
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