Kantonsspital St.Gallen

RAD51 as a potential surrogate marker for DNA repair capacity in solid malignancies

Mariam Gachechiladze, Josef Škarda, Alex Soltermann & Markus Joerger

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.
citation Gachechiladze M, Škarda J, Soltermann A, Joerger M. RAD51 as a potential surrogate marker for DNA repair capacity in solid malignancies. Int J Cancer 2017; 141:1286-1294.
type journal paper/review (English)
date of publishing 19-05-2017
journal title Int J Cancer (141/7)
ISSN electronic 1097-0215
pages 1286-1294
PubMed 28477336
DOI 10.1002/ijc.30764