Delta-like protein 3 expression and therapeutic targeting in neuroendocrine prostate cancer.
Aged
Animals
Antibodies, Monoclonal, Humanized
/ pharmacology
Benzodiazepinones
/ pharmacology
Carcinoma, Neuroendocrine
/ drug therapy
Cell Line, Tumor
Gene Expression Regulation, Neoplastic
/ drug effects
Genetic Heterogeneity
Humans
Immunoconjugates
/ pharmacology
Intracellular Signaling Peptides and Proteins
/ genetics
Male
Membrane Proteins
/ genetics
Mice
Molecular Targeted Therapy
Neoplastic Cells, Circulating
/ metabolism
Prostatic Neoplasms
/ drug therapy
Prostatic Neoplasms, Castration-Resistant
/ drug therapy
Time Factors
Treatment Outcome
Journal
Science translational medicine
ISSN: 1946-6242
Titre abrégé: Sci Transl Med
Pays: United States
ID NLM: 101505086
Informations de publication
Date de publication:
20 03 2019
20 03 2019
Historique:
received:
15
09
2018
accepted:
11
02
2019
entrez:
22
3
2019
pubmed:
22
3
2019
medline:
18
4
2020
Statut:
ppublish
Résumé
Histologic transformation to small cell neuroendocrine prostate cancer occurs in a subset of patients with advanced prostate cancer as a mechanism of treatment resistance. Rovalpituzumab tesirine (SC16LD6.5) is an antibody-drug conjugate that targets delta-like protein 3 (DLL3) and was initially developed for small cell lung cancer. We found that DLL3 is expressed in most of the castration-resistant neuroendocrine prostate cancer (CRPC-NE) (36 of 47, 76.6%) and in a subset of castration-resistant prostate adenocarcinomas (7 of 56, 12.5%). It shows minimal to no expression in localized prostate cancer (1 of 194) and benign prostate (0 of 103). DLL3 expression correlates with neuroendocrine marker expression,
Identifiants
pubmed: 30894499
pii: 11/484/eaav0891
doi: 10.1126/scitranslmed.aav0891
pmc: PMC6525633
mid: NIHMS1019876
pii:
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
Benzodiazepinones
0
DLL3 protein, human
0
Immunoconjugates
0
Intracellular Signaling Peptides and Proteins
0
Membrane Proteins
0
rovalpituzumab tesirine
0
Types de publication
Clinical Trial, Phase I
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NCI NIH HHS
ID : P50 CA090381
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA211024
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA194547
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA210989
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
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