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Updated: Sep 25, 2025

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Delta-like ligand 3 (DLL3): an attractive actionable target in tumors with neuroendocrine origin

Nicoletta Ranallo1, Martine Bocchini2, Jessica Menis3

  • 1Osteoncology and Rare Tumors Center, IRCCS Istituto Romagnolo Per Lo Studio Dei Tumori (IRST) "Dino Amadori", Meldola, Italy.

Expert Review of Anticancer Therapy
|April 28, 2022
PubMed
Abstract

Insights

Neuroendocrine carcinomas are aggressive tumors. Targeting DLL3, a protein on tumor cells, shows promise for new treatments, especially for lung neuroendocrine neoplasms.

Area of Science:

  • Oncology
  • Molecular Biology
  • Immunotherapy

Background:

  • Neuroendocrine carcinomas are aggressive tumors with limited therapeutic options.
  • DLL3 is a transmembrane protein predominantly expressed on neuroendocrine tumor cells, making it a promising therapeutic target.
  • DLL3's role in the tumor microenvironment is increasingly recognized.

Purpose of the Study:

  • To review preclinical and clinical studies on DLL3-targeting strategies in neuroendocrine neoplasms, particularly lung origin.
  • To explore the interaction between DLL3 and the tumor microenvironment.
  • To discuss future directions for DLL3-based therapies.

Main Methods:

  • Literature review of preclinical and clinical studies on DLL3 in neuroendocrine neoplasms.
  • Analysis of the interaction between DLL3 and the tumor microenvironment.
  • Synthesis of current data to propose future research and therapeutic strategies.

Main Results:

  • Various DLL3-targeting strategies have been investigated with variable success.
  • DLL3 influences the tumor (immune) microenvironment.
  • Understanding this interaction is crucial for effective therapy.

Conclusions:

  • DLL3 is a key target for neuroendocrine neoplasms, especially lung origin.
  • Further research into DLL3's role in the tumor microenvironment is essential.
  • Future trials should focus on in vivo diagnostics and novel DLL3-specific therapies.
Keywords:
DLL3Notch pathwayadoptive cell therapiesimmune therapyneuroendocrine carcinomasneuroendocrine tumorstumor microenvironment

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