Prostate Cancer, Version 2.2019, NCCN Clinical Practice Guidelines in Oncology

Journal of the National Comprehensive Cancer Network, Journal Year: 2019, Volume and Issue: 17(5), P. 479 - 505

Published: May 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

Language: Английский

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Prostate cancer

Nature Reviews Disease Primers, Journal Year: 2021, Volume and Issue: 7(1)

Published: Feb. 4, 2021

Language: Английский

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Prostate cancer

The Lancet, Journal Year: 2021, Volume and Issue: 398(10305), P. 1075 - 1090

Published: Aug. 6, 2021

Language: Английский

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PROREPAIR-B: A Prospective Cohort Study of the Impact of Germline DNA Repair Mutations on the Outcomes of Patients With Metastatic Castration-Resistant Prostate Cancer

Journal of Clinical Oncology, Journal Year: 2019, Volume and Issue: 37(6), P. 490 - 503

Published: Jan. 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.

Language: Английский

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The Evolutionary Landscape of Localized Prostate Cancers Drives Clinical Aggression

Cell, Journal Year: 2018, Volume and Issue: 173(4), P. 1003 - 1013.e15

Published: April 19, 2018

Language: Английский

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Interim Results from the IMPACT Study: Evidence for Prostate-specific Antigen Screening in BRCA2 Mutation Carriers

European Urology, Journal Year: 2019, Volume and Issue: 76(6), P. 831 - 842

Published: Sept. 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.

Language: Английский

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Towards precision oncology in advanced prostate cancer

Nature Reviews Urology, Journal Year: 2019, Volume and Issue: 16(11), P. 645 - 654

Published: Oct. 7, 2019

Language: Английский

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BRCA Genes: The Role in Genome Stability, Cancer Stemness and Therapy Resistance

Journal of Cancer, Journal Year: 2019, Volume and Issue: 10(9), P. 2109 - 2127

Published: Jan. 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.

Language: Английский

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The genomic landscape of metastatic castration-resistant prostate cancers reveals multiple distinct genotypes with potential clinical impact

Nature Communications, Journal Year: 2019, Volume and Issue: 10(1)

Published: Nov. 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

Language: Английский

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Patient-derived xenografts and organoids model therapy response in prostate cancer

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: Feb. 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

Language: Английский

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