PMID- 35983951
OWN - NLM
STAT- MEDLINE
DCOM- 20221107
LR  - 20230421
IS  - 1549-490X (Electronic)
IS  - 1083-7159 (Print)
IS  - 1083-7159 (Linking)
VI  - 27
IP  - 11
DP  - 2022 Nov 3
TI  - DLL3 as an Emerging Target for the Treatment of Neuroendocrine Neoplasms.
PG  - 940-951
LID - 10.1093/oncolo/oyac161 [doi]
AB  - INTRODUCTION: Neuroendocrine neoplasms (NEN) are heterogeneous malignancies that 
      can arise at almost any anatomical site and are classified as biologically 
      distinct well-differentiated neuroendocrine tumors (NET) and poorly 
      differentiated neuroendocrine carcinomas (NEC). Current systemic therapies for 
      advanced disease, including targeted therapies, chemotherapy, and immunotherapy, 
      are associated with limited duration of response. New therapeutic targets are 
      needed. One promising target is delta-like ligand 3 (DLL3), an inhibitory ligand 
      of the Notch receptor whose overexpression on the surface of NEN is associated 
      with tumorigenesis. METHODS: This article is a narrative review that highlights 
      the role of DLL3 in NEN progression and prognosis, the potential for therapeutic 
      targeting of DLL3, and ongoing studies of DLL3-targeting therapies. 
      Classification, incidence, pathogenesis, and current management of NEN are 
      reviewed to provide biological context and illustrate the unmet clinical needs. 
      DISCUSSION: DLL3 is overexpressed in many NENs, implicated in tumor progression, 
      and is typically associated with poor clinical outcomes, particularly in patients 
      with NEC. Targeted therapies using DLL3 as a homing beacon for cytotoxic activity 
      mediated via several different mechanisms (eg, antibody-drug conjugates, T-cell 
      engager molecules, CAR-Ts) have shown promising clinical activity in small-cell 
      lung cancer (SCLC). DLL3 may be a clinically actionable target across NEN. 
      CONCLUSIONS: Current treatment options for NEN do not provide sustained 
      responses. DLL3 is expressed on the cell surface of many NEN types and is 
      associated with poor clinical outcomes. Initial clinical studies targeting DLL3 
      therapeutically in SCLC have been promising, and additional studies are expanding 
      this approach to the broader group of NEN.
CI  - (c) The Author(s) 2022. Published by Oxford University Press.
FAU - Yao, James
AU  - Yao J
AUID- ORCID: 0000-0002-1875-3962
AD  - Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer 
      Center, Houston, TX, USA.
FAU - Bergsland, Emily
AU  - Bergsland E
AD  - Department of Medicine, UCSF Helen Diller Family Comprehensive Cancer Center, San 
      Francisco, CA, USA.
FAU - Aggarwal, Rahul
AU  - Aggarwal R
AD  - Department of Medicine, UCSF Helen Diller Family Comprehensive Cancer Center, San 
      Francisco, CA, USA.
FAU - Aparicio, Ana
AU  - Aparicio A
AD  - The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
FAU - Beltran, Himisha
AU  - Beltran H
AD  - Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
FAU - Crabtree, Judy S
AU  - Crabtree JS
AD  - Department of Genetics, Louisiana State University Health Sciences Center, New 
      Orleans, LA, USA.
FAU - Hann, Christine L
AU  - Hann CL
AUID- ORCID: 0000-0002-1467-5557
AD  - Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, 
      MD, USA.
FAU - Ibrahim, Toni
AU  - Ibrahim T
AD  - Osteoncology, Bone and Soft Tissue Sarcomas and Innovative Therapies Unit, IRCSS 
      Istituto Ortopedico Rizzoli, Bologna, Italy.
FAU - Byers, Lauren A
AU  - Byers LA
AD  - Thoracic Head and Neck Medical Oncology, MD Anderson Cancer Center, Houston, TX, 
      USA.
FAU - Sasano, Hironobu
AU  - Sasano H
AUID- ORCID: 0000-0002-6600-8641
AD  - Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, 
      Miyagi, Japan.
FAU - Umejiego, John
AU  - Umejiego J
AD  - Amgen Inc., Thousand Oaks, CA, USA.
FAU - Pavel, Marianne
AU  - Pavel M
AD  - Department of Medicine 1, University Hospital Erlangen, Friedrich-Alexander 
      University Erlangen-Nurnberg, Erlangen, Germany.
LA  - eng
GR  - P30 CA016672/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - England
TA  - Oncologist
JT  - The oncologist
JID - 9607837
RN  - 0 (Ligands)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Membrane Proteins)
RN  - 0 (DLL3 protein, human)
SB  - IM
MH  - Humans
MH  - *Lung Neoplasms/drug therapy
MH  - Ligands
MH  - Intracellular Signaling Peptides and Proteins/genetics
MH  - Membrane Proteins/genetics
MH  - *Small Cell Lung Carcinoma/drug therapy
MH  - *Neuroendocrine Tumors/drug therapy/genetics/pathology
MH  - *Carcinoma, Neuroendocrine/pathology
PMC - PMC9632312
OTO - NOTNLM
OT  - DLL3 protein
OT  - human
OT  - molecular targeted therapy
OT  - neuroendocrine carcinoma
OT  - neuroendocrine tumors
EDAT- 2022/08/20 06:00
MHDA- 2022/11/08 06:00
PMCR- 2022/08/19
CRDT- 2022/08/19 07:22
PHST- 2022/03/30 00:00 [received]
PHST- 2022/07/01 00:00 [accepted]
PHST- 2022/08/20 06:00 [pubmed]
PHST- 2022/11/08 06:00 [medline]
PHST- 2022/08/19 07:22 [entrez]
PHST- 2022/08/19 00:00 [pmc-release]
AID - 6671772 [pii]
AID - oyac161 [pii]
AID - 10.1093/oncolo/oyac161 [doi]
PST - ppublish
SO  - Oncologist. 2022 Nov 3;27(11):940-951. doi: 10.1093/oncolo/oyac161.