Molecular Underpinnings Governing Genetic Complexity of ETS-Fusion-Negative Prostate Cancer.
Cyclin-Dependent Kinases
/ genetics
DNA Repair
ETS Motif
/ genetics
Epigenetic Repression
Gene Expression Regulation, Neoplastic
Genomics
Humans
Loss of Heterozygosity
Male
Molecular Targeted Therapy
/ trends
Nuclear Proteins
/ genetics
Phosphatidylethanolamine Binding Protein
/ pharmacology
Piperazines
/ therapeutic use
Poly (ADP-Ribose) Polymerase-1
/ drug effects
Precision Medicine
/ trends
Prostatic Neoplasms
/ diagnosis
Proteomics
Proto-Oncogene Proteins c-akt
/ antagonists & inhibitors
Proto-Oncogene Proteins c-raf
/ genetics
Pyrimidines
/ therapeutic use
Repressor Proteins
/ genetics
Signal Transduction
Trypsin Inhibitor, Kazal Pancreatic
/ genetics
Journal
Trends in molecular medicine
ISSN: 1471-499X
Titre abrégé: Trends Mol Med
Pays: England
ID NLM: 100966035
Informations de publication
Date de publication:
11 2019
11 2019
Historique:
received:
06
05
2019
revised:
18
06
2019
accepted:
03
07
2019
pubmed:
30
7
2019
medline:
3
7
2020
entrez:
30
7
2019
Statut:
ppublish
Résumé
Inter- and intra-patient molecular heterogeneity of primary and metastatic prostate cancer (PCa) confers variable clinical outcome and poses a formidable challenge in disease management. High-throughput integrative genomics and functional approaches have untangled the complexity involved in this disease and revealed a spectrum of diverse aberrations prevalent in various molecular subtypes, including ETS fusion negative. Emerging evidence indicates that SPINK1 upregulation, mutations in epigenetic regulators or chromatin modifiers, and SPOP are associated with the ETS-fusion negative subtype. Additionally, patients with defects in a DNA-repair pathway respond to poly-(ADP-ribose)-polymerase (PARP) inhibition therapies. Furthermore, a new class of immunogenic subtype defined by CDK12 biallelic loss has also been identified in ETS-fusion-negative cases. This review focuses on the emerging molecular underpinnings driving key oncogenic aberrations and advancements in therapeutic strategies of this disease.
Identifiants
pubmed: 31353123
pii: S1471-4914(19)30175-3
doi: 10.1016/j.molmed.2019.07.001
pmc: PMC7170719
mid: EMS86207
pii:
doi:
Substances chimiques
Nuclear Proteins
0
Phosphatidylethanolamine Binding Protein
0
Piperazines
0
Pyrimidines
0
Repressor Proteins
0
SPOP protein, human
0
Trypsin Inhibitor, Kazal Pancreatic
50936-63-5
ipatasertib
524Y3IB4HQ
Poly (ADP-Ribose) Polymerase-1
EC 2.4.2.30
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
Proto-Oncogene Proteins c-raf
EC 2.7.11.1
CDK12 protein, human
EC 2.7.11.22
Cyclin-Dependent Kinases
EC 2.7.11.22
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
1024-1038Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : DBT-Wellcome Trust India Alliance
ID : IA/I(S)/12/2/500635
Pays : India
Informations de copyright
Copyright © 2019 Elsevier Ltd. All rights reserved.
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