The influence of BRCA2 mutation on localized prostate cancer.

Autor: Taylor RA; Monash Partners Comprehensive Cancer Consortium and Cancer Program, Biomedicine Discovery Institute, Prostate Cancer Research Group, Department of Anatomy and Developmental Biology and Department of Physiology, Monash University, Melbourne, Victoria, Australia.; Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia., Fraser M; Ontario Institute for Cancer Research, Toronto, Ontario, Canada., Rebello RJ; Translational Oncogenomics Group, Cancer Research UK Manchester Institute, The University of Manchester, Manchester Cancer Research Centre, Manchester, UK., Boutros PC; Ontario Institute for Cancer Research, Toronto, Ontario, Canada.; Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.; Department of Pharmacology & Toxicology, University of Toronto, Toronto, Ontario, Canada.; Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.; Departments of Urology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.; Institute for Precision Health, University of California Los Angeles, Los Angeles, CA, USA.; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California Los Angeles, Los Angeles, CA, USA.; Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, CA, USA., Murphy DG; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia.; Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia., Bristow RG; Translational Oncogenomics Group, Cancer Research UK Manchester Institute, The University of Manchester, Manchester Cancer Research Centre, Manchester, UK., Risbridger GP; Monash Partners Comprehensive Cancer Consortium and Cancer Program, Biomedicine Discovery Institute, Prostate Cancer Research Group, Department of Anatomy and Developmental Biology and Department of Physiology, Monash University, Melbourne, Victoria, Australia. gail.risbridger@monash.edu.; Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia. gail.risbridger@monash.edu.; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia. gail.risbridger@monash.edu.
Jazyk: angličtina
Zdroj: Nature reviews. Urology [Nat Rev Urol] 2019 May; Vol. 16 (5), pp. 281-290.
DOI: 10.1038/s41585-019-0164-8
Abstrakt: A key challenge in the management of localized prostate cancer is the identification of men with a high likelihood of progression to an advanced, incurable stage. Patients who harbour germline BRCA2 mutations have worse clinical outcomes than noncarriers when treated with surgery or radiotherapy. Insights from different disciplines have improved our understanding of why patients with BRCA2-mutant tumours have a high likelihood of failing on conventional management after diagnosis. Treatment-naive BRCA2-mutant tumours are defined by aggressive clinical and molecular features early in the disease course, and the genomic landscape of these BRCA2-mutant tumours is characterized by a unique molecular profile and higher genomic instability than noncarrier tumours. Moreover, BRCA2-mutant tumours commonly show the concurrent presence of the intraductal carcinoma of the prostate (IDCP) pathology, a poor prognostic indicator. Subclonal analyses have revealed that IDCP and invasive adenocarcinoma in BRCA2-mutant tumours can arise from the same ancestral clone, implying that a temporal evolutionary trajectory exists. Finally, functional studies have shown that BRCA2-mutant tumours can harbour a subpopulation of cancer cells that can tolerate castration de novo, enabling the tumour to evade androgen deprivation therapy. Importantly, future challenges remain regarding how to best model the biology underpinning this aggressive phenotype and translate these findings to improve clinical outcomes.
Databáze: MEDLINE
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