Circulating Tumor Cell Genomic Evolution and Hormone Therapy Outcomes in Men with Metastatic Castration-Resistant Prostate Cancer.
Aged
Aged, 80 and over
Androstenes
/ administration & dosage
Antineoplastic Combined Chemotherapy Protocols
/ therapeutic use
Benzamides
/ administration & dosage
Clinical Trials as Topic
Drug Resistance, Neoplasm
/ genetics
Genomics
/ methods
Humans
Male
Middle Aged
Multicenter Studies as Topic
Neoplasm Metastasis
Neoplastic Cells, Circulating
/ metabolism
Nitriles
/ administration & dosage
Phenylthiohydantoin
/ administration & dosage
Prostatic Neoplasms, Castration-Resistant
/ drug therapy
Protein Isoforms
/ genetics
Receptors, Androgen
/ genetics
Retrospective Studies
Treatment Outcome
Journal
Molecular cancer research : MCR
ISSN: 1557-3125
Titre abrégé: Mol Cancer Res
Pays: United States
ID NLM: 101150042
Informations de publication
Date de publication:
06 2021
06 2021
Historique:
received:
11
11
2020
revised:
11
01
2021
accepted:
01
03
2021
pubmed:
28
3
2021
medline:
27
1
2022
entrez:
27
3
2021
Statut:
ppublish
Résumé
Men with circulating tumor cell (CTC) AR-V7-positive metastatic castration-resistant prostate cancer (mCRPC) have worse outcomes when treated with enzalutamide/abiraterone. However, most men lack CTC AR-V7 detection, and additional predictive biomarkers are needed. We conducted a retrospective secondary analysis of the prospective PROPHECY trial (NCT02269982) of men with mCRPC undergoing treatment with enzalutamide/abiraterone, analyzing pooled CTC and germline DNA for whole-genome copy-number alterations (CNA) in 73 samples from 48 men over time along with pooled CTC and germline whole-exome sequencing on 22 paired samples before and following progression on androgen receptor (AR) inhibitor therapy to identify somatic genomic alterations associated with acquired resistance. We observed broad interpatient and longitudinal CTC genomic heterogeneity from AR-V7-negative men with mCRPC, including common gains of
Identifiants
pubmed: 33771885
pii: 1541-7786.MCR-20-0975
doi: 10.1158/1541-7786.MCR-20-0975
pmc: PMC8178231
mid: NIHMS1682354
doi:
Substances chimiques
Androstenes
0
Benzamides
0
Nitriles
0
Protein Isoforms
0
Receptors, Androgen
0
Phenylthiohydantoin
2010-15-3
enzalutamide
93T0T9GKNU
abiraterone
G819A456D0
Banques de données
ClinicalTrials.gov
['NCT02269982']
ChiCTR
['NCT02204943']
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1040-1050Subventions
Organisme : NCI NIH HHS
ID : P30 CA014236
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA233585
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA256157
Pays : United States
Organisme : NCI NIH HHS
ID : R21 CA216800
Pays : United States
Informations de copyright
©2021 American Association for Cancer Research.
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