Graphical summary. Credit score: Cell Reviews Medication (2025). DOI: 10.1016/j.xcrm.2025.101937
Printed in Cell Reviews Medication, outcomes of a VHIO-led research assist the feasibility of utilizing RAD51 testing to enrich next-generation sequencing (NGS) for exact affected person stratification and remedy choice in metastatic prostate most cancers (mPC).
Totally different genomic alterations in DNA harm restore (DDR) pathways happen in 20% to 25% of superior prostate most cancers, together with homologous recombination restore (HRR) gene alterations. Figuring out the molecular traits and targetable mutations of every tumor has turn out to be an integral a part of metastatic prostate most cancers care.
“The association of homologous recombination repair defects with response to treatment with PARP inhibitors marked the first successful application of precision medicine in patients with prostate cancer,” mentioned Joaquin Mateo, a medical oncologist on the Vall d’Hebron College Hospital, co-leader of VHIO’s Prostate Most cancers Group, and co-corresponding creator of this research.
“However, several challenges of NGS testing still impede the widespread implementation of precision medicine in routine metastatic prostate cancer care,” added Mateo.
“Refining cancer biomarker strategies and identifying new tumor markers that complement current NGS methods could facilitate a more precise patient stratification and treatment selection process” mentioned Violeta Serra, Head of VHIO’s Experimental Therapeutics Group and co-corresponding creator of this current article.
RAD51 is a protein concerned in homologous recombination restore (HRR) alterations. Developed in-house by Serra’s laboratory, the RAD51 assay relies on the detection of this protein as a purposeful biomarker to doubtlessly improve the stratification of sufferers with most cancers related to deficiency on this DNA harm restore (DDR) pathway.
Practical assays that may detect dynamic adjustments in HRR capability may additionally assist affected person stratification methods and assist prioritize NGS testing when assets are restricted.
Complete evaluation of DNA harm
For this research, the investigators carried out a complete evaluation of homologous recombination restore standing by way of parallel analysis utilizing NGS and the RAD51 take a look at in 219 main or metastatic biopsies from 187 sufferers with superior prostate most cancers.
Genomic evaluation revealed that essentially the most often altered genes included TP53, PTEN, AR, MYC, BRCA2, ATM and BRCA1, highlighting the complicated genomic panorama of mCRC.
RAD51 immunofluorescence confirmed that 21% of evaluable samples had a RAD51-low rating, indicating HRR deficiency, and a excessive sensitivity and specificity for figuring out tumors with BRCA1/2 alterations. Sufferers with RAD51-low scores skilled longer development free survival (PFS) on remedy with PARP inhibitors or platinum chemotherapy.
“Our results demonstrate the feasibility of using the RAD51 biomarker to identify patients with homologous recombination repair-defective prostate cancer and who may therefore be sensitive to treatment with PARP inhibitors,” mentioned Serra.
“This biomarker could complement NGS in clinical practice, particularly in cases with limited tissue availability where sequencing may not be possible,” concluded Mateo.
Extra data:
Sara Arce-Gallego et al, Homologous recombination restore standing in metastatic prostate most cancers by next-generation sequencing and purposeful immunofluorescence, Cell Reviews Medication (2025). DOI: 10.1016/j.xcrm.2025.101937
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Vall d’Hebron Institute of Oncology
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RAD51 biomarker may complement next-generation sequencing in personalizing prostate most cancers remedy (2025, February 5)
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