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A microscope test on an ordinary tumour biopsy that counts RAD51 repair spots in dividing cells; few spots means the tumour cannot repair DNA by homologous recombination right now, which is what PARP inhibitors exploit.
What it measures. RAD51 is the protein that carries out homologous recombination repair. When repair is working, cells that have replicated their DNA show nuclear RAD51 foci after damage; when BRCA1, BRCA2, PALB2 or another repair gene is lost, the foci do not form. The assay stains a routine formalin-fixed slide for RAD51 and geminin (a marker of the cells that should be repairing) and reports the share of geminin-positive cells with RAD51 foci. A low score is a functional read-out of homologous recombination deficiency at the moment of the biopsy.
Who should have it. It is being studied in the same settings as genomic HRD tests: high-grade serous ovarian cancer, triple-negative and BRCA-associated breast cancer, and metastatic prostate cancer, where the question is whether a PARP inhibitor or platinum will work. Unlike a genomic scar, which stays behind after resistance has developed, RAD51 foci return when repair is restored, so the assay may also identify patients whose tumours have become resistant.
Evidence. The Vall d'Hebron group showed that a RAD51 score measured in routine samples predicted PARP inhibitor response in patient-derived xenografts beyond BRCA mutation (EMBO Molecular Medicine 2018) and later linked low RAD51 to benefit from platinum in the GeparSixto breast cancer trial. Prospective trials selecting patients on RAD51 are ongoing. The assay is a research and academic laboratory test; no version has regulatory clearance as a companion diagnostic.
What changes. Today, nothing formally: treatment decisions still rest on BRCA sequencing and genomic scar scores. If validated, a low RAD51 score would widen PARP inhibitor use to tumours with no BRCA mutation and a negative scar score, and a high score after progression would argue against continuing them. Cost is that of an immunohistochemistry stain plus specialised scoring, and availability is limited to research centres.
Immunofluorescence for RAD51 and geminin on formalin-fixed tumour sections; the fraction of geminin-positive (S/G2) cells with five or more nuclear RAD51 foci scores current homologous recombination capacity.
Query for this technology: (TITLE:"RAD51 foci assay" OR ABSTRACT:"RAD51 foci assay" OR TITLE:"functional HRD test" OR ABSTRACT:"functional HRD test" OR TITLE:"RAD51 assay" OR ABSTRACT:"RAD51 assay" OR TITLE:"RAD51 immunofluorescence" OR ABSTRACT:"RAD51 immunofluorescence") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about RAD51 foci assay (functional HRD test), not a curated reading list.
Shares HRD genomic scar scores (GIS, LOH, HRDetect), HRD & BRCA testing, Niraparib, Homologous recombination deficiency (HRD).
Shares HRD & BRCA testing, Homologous recombination deficiency (HRD), PARP, PARP inhibitors.
Shares Rucaparib, Talazoparib, Niraparib, Homologous recombination deficiency (HRD).
Shares Rucaparib, High-grade serous ovarian cancer, Niraparib, Homologous recombination deficiency (HRD).
Shares HRD & BRCA testing, Talazoparib, Companion diagnostics, PARP.
Shares HRD genomic scar scores (GIS, LOH, HRDetect), High-grade serous ovarian cancer, Homologous recombination deficiency (HRD), PARP.
Shares HRD genomic scar scores (GIS, LOH, HRDetect), High-grade serous ovarian cancer, Niraparib, Homologous recombination deficiency (HRD).
Shares HRD & BRCA testing, High-grade serous ovarian cancer, Homologous recombination deficiency (HRD), PARP.