Sistema de Salut de Catalunya
Institut Català de la Salut
[Nombela P] Prostate Cancer Clinical Research Unit, Spanish National Cancer Research Center, Madrid, Spain. [Lozano R, Olmos D] Prostate Cancer Clinical Research Unit, Spanish National Cancer Research Center, Madrid, Spain. CNIO-IBIMA Genitourinary Cancer Research Unit, Institute of Biomedical Research in Malaga (IBIMA), Málaga, Spain. [Aytes A] Programs of Molecular Mechanisms and Experimental Therapeutics in Oncology (ONCOBell), and Cancer Therapeutics Resistance (ProCURE), Catalan Institute of Oncology, Bellvitge Institute for Biomedical Research, L'Hospitalet de Llobregat, Spain. [Mateo J] Vall d'Hebron Institut d'Oncologia, Barcelona, Spain. Hospital Universitari Vall d'Hebron, Barcelona, Spain. [Castro] Prostate Cancer Clinical Research Unit, Spanish National Cancer Research Center, Madrid, Spain. Medical Oncology Department, Hospital Universitario Quironsalud Madrid, Madrid, Spain.
Vall d'Hebron Barcelona Hospital Campus
2019-05-20T07:44:44Z
2019-05-20T07:44:44Z
2019-03-12
BRCA2; DDR; Prostate cancer
BRCA2; DDR; Càncer de pròstata
BRCA2; DDR; Cáncer de próstata
Germline and somatic aberrations in DNA damage repair (DDR) genes are more prevalent in prostate cancer than previously recognized, with BRCA2 as the most commonly altered gene. Germline mutations in BRCA2 have been linked to poor prognosis when patients are managed under the protocols currently approved for prostate cancer. The impact of germline mutations in other DDR genes beyond BRCA2 remain unclear. Importantly, a quarter of prostate cancer patients identified as germline mutation carriers lack a family history of cancer. The clinical implications of somatic DDR defects are yet to be elucidated. Poly ADP-ribose polymerase (PARP) inhibitors and platinum-based chemotherapy have proven to be effective in the treatment of other tumor types linked to BRCA1 and BRCA2 alterations and several trials are currently evaluating their efficacy in prostate cancer. Here, we summarize the available evidence regarding the prevalence of somatic and germline DDR defects in prostate cancer; their association with clinical outcomes; the trials assessing the efficacy of new therapies that exploit DDR defects in prostate cancer and briefly discuss some uncertainties about the most appropriate management for these patients.
Supported by grants CM17/00221, PI16/01070, CP15/00090 and PI16/01565 from the Instituto de Salud Carlos III, PC170510P2 from the U.S. Department of Defense, W81XWH-18-1-0193 from the U.S. Department of Defense, RYC-2015-18625 from the Ministerio de Economía y Competitividad and Young Investigator Awards from the Prostate Cancer Foundation
Article
Published version
English
Pròstata - Càncer- Aspectes genètics; ADN - Dany; ADN - Reparació; DISEASES::Neoplasms::Neoplasms by Site::Urogenital Neoplasms::Genital Neoplasms, Male::Prostatic Neoplasms; CHEMICALS AND DRUGS::Amino Acids, Peptides, and Proteins::Proteins::Fanconi Anemia Complementation Group Proteins::BRCA2 Protein; PHENOMENA AND PROCESSES::Genetic Phenomena::DNA Damage; PHENOMENA AND PROCESSES::Chemical Phenomena::Biochemical Phenomena::DNA Repair; Other subheadings::Other subheadings::Other subheadings::/genetics; ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias urogenitales::neoplasias de los genitales masculinos::neoplasias de la próstata; COMPUESTOS QUÍMICOS Y DROGAS::aminoácidos, péptidos y proteínas::proteínas::proteínas de grupos de complementación de la anemia de Fanconi::proteína BRCA2; FENÓMENOS Y PROCESOS::fenómenos genéticos::daño del ADN; FENÓMENOS Y PROCESOS::fenómenos químicos::fenómenos bioquímicos::reparación del ADN; Otros calificadores::Otros calificadores::Otros calificadores::/genética
MDPI
Cancers;11(3)
https://www.mdpi.com/2072-6694/11/3/352
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
