Epigenetic
Animals
Carbamates
/ pharmacology
Carcinoma, Neuroendocrine
/ drug therapy
Cetuximab
/ pharmacology
Colonic Neoplasms
/ drug therapy
Drug Resistance, Neoplasm
Epigenesis, Genetic
ErbB Receptors
/ antagonists & inhibitors
Humans
Mice
Mice, Inbred NOD
Mice, SCID
Mutation
Protein Kinase Inhibitors
/ pharmacology
Proto-Oncogene Proteins B-raf
/ antagonists & inhibitors
Sulfonamides
/ pharmacology
Treatment Outcome
Xenograft Model Antitumor Assays
Journal
Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN: 1557-3265
Titre abrégé: Clin Cancer Res
Pays: United States
ID NLM: 9502500
Informations de publication
Date de publication:
15 02 2020
15 02 2020
Historique:
received:
18
04
2019
revised:
12
08
2019
accepted:
21
10
2019
pubmed:
2
11
2019
medline:
18
11
2020
entrez:
2
11
2019
Statut:
ppublish
Résumé
The limited knowledge of the molecular alterations that characterize poorly differentiated neuroendocrine carcinomas has limited the clinical development of targeted agents directed to driver mutations. Here we aim to identify new molecular targets in colon neuroendocrine carcinomas (co-NEC) and proof the efficacy of matching drugs. We performed a multi-omic analysis of co-NEC to identify genetic or epigenetic alterations that could be exploited as effective drug targets. We compared co-NEC samples with colorectal carcinomas (CRC) to identify neuroendocrine-specific traits. Patients with co-NEC and patient-derived xenografts were treated with a BRAFV600E-blocking drug to demonstrate sensitivity. co-NEC and CRC are similar in their mutational repertoire, although co-NECs are particularly enriched in The identification of
Identifiants
pubmed: 31672771
pii: 1078-0432.CCR-19-1266
doi: 10.1158/1078-0432.CCR-19-1266
doi:
Substances chimiques
Carbamates
0
Protein Kinase Inhibitors
0
Sulfonamides
0
encorafenib
8L7891MRB6
EGFR protein, human
EC 2.7.10.1
ErbB Receptors
EC 2.7.10.1
BRAF protein, human
EC 2.7.11.1
Proto-Oncogene Proteins B-raf
EC 2.7.11.1
Cetuximab
PQX0D8J21J
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
902-909Informations de copyright
©2019 American Association for Cancer Research.