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Theranostic biomarkers of PARP inhibitors: current recommendations and organisational challenges for French laboratories

Par : Contributeur(s) : Type de matériel : TexteTexteLangue : français Détails de publication : 2025. Ressources en ligne : Abrégé : In recent years, PARP inhibitors (iPARP) represent a novel therapeutic option for cancers with homologous recombination deficiency, such as ovarian, breast, pancreatic, and prostate cancers. Identifying biomarkers that predict response to iPARP is crucial for selecting patients who will benefit the most from this treatment. The detection of deleterious variants in BRCA1 and BRCA2 genes and/or genomic instability is now recognised as theranostic biomarkers for iPARP. These biomarkers can be tested together using composite HRD tests, which must be validated both analytically and clinically. Numerous emerging biomarkers are being studied (including deleterious variants in HRR genes other than BRCA, hypermethylation of the BRCA1, RAD51C, and PALB2 gene promoters, RAD51 foci accumulation) and could become standard practice in the future if their clinical utility can be demonstrated. Testing strategies (constitutional/tumoral) may differ between institutions but should align with current iPARP indications. For tumour-based tests, strict pre-analytical conditions are needed to ensure reliable results. Funding of these companion diagnostic assays is evolving in France, as illustrated by the creation of a novel nomenclature for the reimbursement of HRD tests in September 2024.
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In recent years, PARP inhibitors (iPARP) represent a novel therapeutic option for cancers with homologous recombination deficiency, such as ovarian, breast, pancreatic, and prostate cancers. Identifying biomarkers that predict response to iPARP is crucial for selecting patients who will benefit the most from this treatment. The detection of deleterious variants in BRCA1 and BRCA2 genes and/or genomic instability is now recognised as theranostic biomarkers for iPARP. These biomarkers can be tested together using composite HRD tests, which must be validated both analytically and clinically. Numerous emerging biomarkers are being studied (including deleterious variants in HRR genes other than BRCA, hypermethylation of the BRCA1, RAD51C, and PALB2 gene promoters, RAD51 foci accumulation) and could become standard practice in the future if their clinical utility can be demonstrated. Testing strategies (constitutional/tumoral) may differ between institutions but should align with current iPARP indications. For tumour-based tests, strict pre-analytical conditions are needed to ensure reliable results. Funding of these companion diagnostic assays is evolving in France, as illustrated by the creation of a novel nomenclature for the reimbursement of HRD tests in September 2024.

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