دورية أكاديمية

How the Analysis of the Pathogenetic Variants of DDR Genes Will Change the Management of Prostate Cancer Patients

التفاصيل البيبلوغرافية
العنوان: How the Analysis of the Pathogenetic Variants of DDR Genes Will Change the Management of Prostate Cancer Patients
المؤلفون: Alessandro Sciarra, Marco Frisenda, Giulio Bevilacqua, Alessandro Gentilucci, Susanna Cattarino, Gianna Mariotti, Francesco Del Giudice, Giovanni Battista Di Pierro, Pietro Viscuso, Paolo Casale, Benjamin I. Chung, Riccardo Autorino, Simone Crivellaro, Stefano Salciccia
المصدر: International Journal of Molecular Sciences; Volume 24; Issue 1; Pages: 674
بيانات النشر: Multidisciplinary Digital Publishing Institute
سنة النشر: 2022
المجموعة: MDPI Open Access Publishing
مصطلحات موضوعية: prostate neoplasm, PARP inhibitor, BRCA gene, DDR gene, castration-resistant
جغرافية الموضوع: agris
الوصف: Herein, we analyze answers achieved, open questions, and future perspectives regarding the analysis of the pathogenetic variants (PV) of DNA damage response (and repair) (DDR) genes in prostate cancer (PC) patients. The incidence of PVs in homologous recombination repair (HRR) genes among men with metastatic PC varied between 11% and 33%, which was significantly higher than that in non-metastatic PC, and BRCA2 mutations were more frequent when compared to other DDR genes. The determination of the somatic or germline PVs of BRCA2 was able to define a tailored therapy using PARP inhibitors in metastatic castration-resistant prostate cancer (mCRPC) progression after first-line therapy, with significant improvements in the radiologic progression-free survival (rPFS) and overall survival (OS) rates. We propose testing all metastatic PC patients for somatic and germline HRR mutations. Somatic determination on the primary site or on historic paraffin preparations with a temporal distance of no longer than 5 years should be preferred over metastatic site biopsies. The prognostic use of DDR PVs will also be used in selected high-risk cases with non-metastatic stages to better arrange controls and therapeutic primary options. We anticipate that the use of poly-ADP-ribose polymerase (PARP) inhibitors in hormone-sensitive prostate cancer (HSPC) and in combination with androgen receptor signaling inhibitors (ARSI) will be new strategies.
نوع الوثيقة: text
وصف الملف: application/pdf
اللغة: English
العلاقة: Molecular Oncology; https://dx.doi.org/10.3390/ijms24010674Test
DOI: 10.3390/ijms24010674
الإتاحة: https://doi.org/10.3390/ijms24010674Test
حقوق: https://creativecommons.org/licenses/by/4.0Test/
رقم الانضمام: edsbas.FB9647E8
قاعدة البيانات: BASE