Chromatin profiles classify castration-resistant prostate cancers suggesting therapeutic targets.
Science
; 376(6596): eabe1505, 2022 05 27.
Article
em En
| MEDLINE
| ID: mdl-35617398
ABSTRACT
In castration-resistant prostate cancer (CRPC), the loss of androgen receptor (AR) dependence leads to clinically aggressive tumors with few therapeutic options. We used ATAC-seq (assay for transposase-accessible chromatin sequencing), RNA-seq, and DNA sequencing to investigate 22 organoids, six patient-derived xenografts, and 12 cell lines. We identified the well-characterized AR-dependent and neuroendocrine subtypes, as well as two AR-negative/low groups a Wnt-dependent subtype, and a stem cell-like (SCL) subtype driven by activator protein-1 (AP-1) transcription factors. We used transcriptomic signatures to classify 366 patients, which showed that SCL is the second most common subtype of CRPC after AR-dependent. Our data suggest that AP-1 interacts with the YAP/TAZ and TEAD proteins to maintain subtype-specific chromatin accessibility and transcriptomic landscapes in this group. Together, this molecular classification reveals drug targets and can potentially guide therapeutic decisions.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Cromatina
/
Terapia de Alvo Molecular
/
Neoplasias de Próstata Resistentes à Castração
Tipo de estudo:
Prognostic_studies
Limite:
Humans
/
Male
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article