Mini Review
RAD51 as a potential surrogate marker for DNA repair capacity in solid malignancies
Mariam Gachechiladze,
Josef Škarda,
Alex Soltermann,
Markus Joerger,
Mariam Gachechiladze
Department of Clinical and Molecular Pathology, Institute of Translational and Molecular Medicine, Faculty of Medicine and Dentistry, Palacký University, Olomouc, Czech Republic
M.G. and J.Š. share first authorship
Search for more papers by this authorJosef Škarda
Department of Clinical and Molecular Pathology, Institute of Translational and Molecular Medicine, Faculty of Medicine and Dentistry, Palacký University, Olomouc, Czech Republic
M.G. and J.Š. share first authorship
Search for more papers by this authorAlex Soltermann
Department of Pathology and Molecular Pathology, University Hospital, Zurich, Switzerland
Search for more papers by this authorCorresponding Author
Markus Joerger
Department of Medical Oncology and Hematology, Cantonal Hospital, St.Gallen, Switzerland
Correspondence to: Markus Joerger, MD-PhD, ClinPharm, Department of Medical Oncology & Hematology, Cantonal Hospital St.Gallen, CH-9007 St.Gallen, Switzerland, Tel.: +41-765591070, E-mail: [email protected]Search for more papers by this authorMariam Gachechiladze,
Josef Škarda,
Alex Soltermann,
Markus Joerger,
Mariam Gachechiladze
Department of Clinical and Molecular Pathology, Institute of Translational and Molecular Medicine, Faculty of Medicine and Dentistry, Palacký University, Olomouc, Czech Republic
M.G. and J.Š. share first authorship
Search for more papers by this authorJosef Škarda
Department of Clinical and Molecular Pathology, Institute of Translational and Molecular Medicine, Faculty of Medicine and Dentistry, Palacký University, Olomouc, Czech Republic
M.G. and J.Š. share first authorship
Search for more papers by this authorAlex Soltermann
Department of Pathology and Molecular Pathology, University Hospital, Zurich, Switzerland
Search for more papers by this authorCorresponding Author
Markus Joerger
Department of Medical Oncology and Hematology, Cantonal Hospital, St.Gallen, Switzerland
Correspondence to: Markus Joerger, MD-PhD, ClinPharm, Department of Medical Oncology & Hematology, Cantonal Hospital St.Gallen, CH-9007 St.Gallen, Switzerland, Tel.: +41-765591070, E-mail: [email protected]Search for more papers by this authorConflict of Interest Statement: None declared.
Abstract
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.
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