Nature, Год журнала: 2022, Номер 609(7927), С. 552 - 559
Опубликована: Авг. 31, 2022
Prostate cancer is characterized by considerable geo-ethnic disparity. African ancestry a significant risk factor, with mortality rates across sub-Saharan Africa of 2.7-fold higher than global averages
Язык: Английский
Journal of the National Comprehensive Cancer Network, Год журнала: 2019, Номер 17(5), С. 479 - 505
Опубликована: Май 1, 2019
The NCCN Guidelines for Prostate Cancer include recommendations regarding diagnosis, risk stratification and workup, treatment options localized disease, management of recurrent advanced disease clinicians who treat patients with prostate cancer. portions the guidelines included herein focus on roles germline somatic genetic testing, nomograms tumor multigene molecular androgen deprivation therapy, secondary hormonal chemotherapy, immunotherapy in
Язык: Английский
Процитировано
1435
Nature Reviews Disease Primers, Год журнала: 2021, Номер 7(1)
Опубликована: Фев. 4, 2021
Язык: Английский
Процитировано
749
The Lancet, Год журнала: 2021, Номер 398(10305), С. 1075 - 1090
Опубликована: Авг. 6, 2021
Язык: Английский
Процитировано
399
Journal of Clinical Oncology, Год журнала: 2019, Номер 37(6), С. 490 - 503
Опубликована: Янв. 9, 2019
Germline mutations in DNA damage repair (DDR) genes are identified a significant proportion of patients with metastatic prostate cancer, but the clinical implications these remain unclear. This prospective multicenter cohort study evaluated prevalence and effect germline DDR (gDDR) on castration-resistance cancer (mCRPC) outcomes.Unselected were enrolled at diagnosis mCRPC screened for gDDR 107 genes. The primary aim was to assess impact ATM/BRCA1/BRCA2/ PALB2 cause-specific survival (CSS) from mCRPC. Secondary aims included association subgroups response outcomes treatments. Combined progression-free first systemic therapy (PFS) until progression second (PFS2) also explored.We 68 carriers (16.2%) 419 eligible patients, including 14 BRCA2, eight ATM, four BRCA1, none mutations. did not reach its end point, because difference CSS between ATM/BRCA1/BRCA2/PALB2 noncarriers statistically (23.3 v 33.2 months; P = .264). halved BRCA2 (g BRCA2) (17.4 .027), g as an independent prognostic factor CCS (hazard ratio [HR], 2.11; .033). Significant interactions status treatment type (androgen signaling inhibitor taxane therapy) observed (CSS adjusted .014; PFS2 .005). (24.0 17.0 months) (18.9 8.6 greater treated line abiraterone or enzalutamide compared taxanes. Clinical differ by noncarriers.g have deleterious that may be affected used. Determination assistance selection initial Nonetheless, confirmatory studies required before results can support change practice.
Язык: Английский
Процитировано
330
Cell, Год журнала: 2018, Номер 173(4), С. 1003 - 1013.e15
Опубликована: Апрель 19, 2018
Язык: Английский
Процитировано
219
European Urology, Год журнала: 2019, Номер 76(6), С. 831 - 842
Опубликована: Сен. 17, 2019
Mutations in BRCA2 cause a higher risk of early-onset aggressive prostate cancer (PrCa). The IMPACT study is evaluating targeted PrCa screening using prostate-specific-antigen (PSA) men with germline BRCA1/2 mutations.
Язык: Английский
Процитировано
202
Nature Reviews Urology, Год журнала: 2019, Номер 16(11), С. 645 - 654
Опубликована: Окт. 7, 2019
Язык: Английский
Процитировано
196
Journal of Cancer, Год журнала: 2019, Номер 10(9), С. 2109 - 2127
Опубликована: Янв. 1, 2019
Carcinogenesis is a multistep process, and tumors frequently harbor multiple mutations regulating genome integrity, cell division death.The integrity of cellular closely controlled by the mechanisms DNA damage signaling repair.The association breast cancer susceptibility genes BRCA1 BRCA2 with ovarian development was first demonstrated over 20 years ago.Since then germline within these were linked to genomic instability increased risk many other types.Genomic an engine oncogenic transformation non-tumorigenic cells into tumor-initiating further tumor evolution.In this review we discuss biological functions role BRCA in initiation, regulation stemness, therapy resistance progression.
Язык: Английский
Процитировано
184
Nature Communications, Год журнала: 2019, Номер 10(1)
Опубликована: Ноя. 20, 2019
Metastatic castration-resistant prostate cancer (mCRPC) has a highly complex genomic landscape. With the recent development of novel treatments, accurate stratification strategies are needed. Here we present whole-genome sequencing (WGS) analysis fresh-frozen metastatic biopsies from 197 mCRPC patients. Using unsupervised clustering based on features, define eight distinct clusters. We observe potentially clinically relevant genotypes, including microsatellite instability (MSI), homologous recombination deficiency (HRD) enriched with deletions and BRCA2 aberrations, tandem duplication genotype associated CDK12
Язык: Английский
Процитировано
184
Nature Communications, Год журнала: 2021, Номер 12(1)
Опубликована: Фев. 18, 2021
Abstract Therapy resistance and metastatic processes in prostate cancer (PCa) remain undefined, due to lack of experimental models that mimic different disease stages. We describe an androgen-dependent PCa patient-derived xenograft (PDX) model from treatment-naïve, soft tissue metastasis (PNPCa). RNA whole-exome sequencing the PDX organoids confirmed transcriptomic genomic similarity primary tumor. PNPCa harbors BRCA2 CHD1 somatic mutations, shows SPOP/FOXA1 -like signature microsatellite instability, which occurs 3% advanced has never been modeled vivo. Comparison treatment-naïve with additional PDXs (BM18, LAPC9), a medium-throughput organoid screen FDA-approved compounds, revealed differential drug sensitivities. Multikinase inhibitors (ponatinib, sunitinib, sorafenib) were broadly effective on all PDX- cases acquired standard-of-care compounds. This proof-of-principle study may provide preclinical tool responses newly identified, repurposed
Язык: Английский
Процитировано
119