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RAD51 as a potential surrogate marker for DNA repair capacity in solid malignancies
Author(s) -
Gachechiladze Mariam,
Škarda Josef,
Soltermann Alex,
Joerger Markus
Publication year - 2017
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.30764
Subject(s) - rad51 , dna repair , radioresistance , biology , dna damage , homologous recombination , dna , cancer research , olaparib , poly adp ribose polymerase , computational biology , genetics , polymerase , cell culture
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.