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Updated: Jan 26, 2026

Ex Vivo Treatment Response of Primary Tumors and/or Associated Metastases for Preclinical and Clinical Development of Therapeutics
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Notch pathway in small-cell lung cancer: from preclinical evidence to therapeutic challenges

Alessandro Leonetti1,2, Francesco Facchinetti3,4, Roberta Minari3

  • 1Medical Oncology Unit, University Hospital of Parma, 43126, Parma, Italy. alessandroleonetti@hotmail.com.

Cellular Oncology (Dordrecht, Netherlands)
|April 11, 2019
PubMed
Abstract

Insights

Small-cell lung cancer (SCLC) recurrence is common, but targeting delta-like protein 3 (DLL3) shows promise. The DLL3-targeted antibody-drug conjugate rovalpituzumab tesirine offers a new therapeutic strategy for SCLC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • Small-cell lung cancer (SCLC) is an aggressive malignancy with limited treatment options and frequent recurrence.
  • Notch pathway deregulation, particularly delta-like protein 3 (DLL3) expression, is crucial in SCLC development, progression, and chemoresistance.
  • DLL3 is highly expressed in SCLC (~85%) but minimally in normal lung tissue, making it a promising biomarker and therapeutic target.

Purpose of the Study:

  • To review the biological role of Notch signaling in SCLC.
  • To discuss the clinical implications of targeting DLL3 in SCLC.
  • To highlight novel therapeutic approaches for SCLC.

Main Methods:

  • Review of preclinical findings on Notch signaling in SCLC.
  • Analysis of clinical data for DLL3-targeted therapies.
  • Discussion of current and future therapeutic strategies.

Main Results:

  • Notch pathway deregulation is a key event in SCLC tumorigenesis and progression.
  • DLL3 is a highly specific biomarker and target for SCLC.
  • Rovalpituzumab tesirine (Rova-T) demonstrates promising efficacy and safety in extensive SCLC.

Conclusions:

  • DLL3-targeted therapies, such as rovalpituzumab tesirine, represent a novel and effective approach for SCLC management.
  • Targeting DLL3 combines specific SCLC targeting with potent cytotoxic cell killing.
  • Further clinical studies are warranted to explore the full potential of DLL3-targeted therapies in SCLC.
Keywords:
DLL3Notch pathwayRovalpituzumab tesirineSmall cell lung cancer (SCLC)

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