Analysis of DLL3 and ASCL1 in Surgically Resected Small Cell Lung Cancer (HOT1702)

Megumi Furuta1, Jun Sakakibara-Konishi2, Hajime Kikuchi3

  • 1Department of Respiratory Medicine, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.

The Oncologist
|May 10, 2019
PubMed
Abstract

Insights

Delta-like protein 3 (DLL3) and ASCL1 are highly expressed in small cell lung cancer (SCLC). These proteins may serve as therapeutic targets for SCLC treatment, including with Rova-T.

Area of Science:

  • Oncology
  • Molecular Biology

Background:

  • Delta-like protein 3 (DLL3) is a Notch ligand implicated in small cell lung cancer (SCLC) tumorigenesis.
  • ASCL1 is a transcription factor involved in pulmonary neuroendocrine cell development and regulates DLL3 expression.
  • Rovalpituzumab tesirine (Rova-T) is a novel DLL3-targeted antibody-drug conjugate for SCLC treatment.

Purpose of the Study:

  • To investigate the expression of DLL3 and ASCL1 in surgically resected SCLC samples.
  • To determine the correlation between DLL3 and ASCL1 expression and clinicopathological features.
  • To explore the potential of DLL3 and ASCL1 as therapeutic targets in SCLC.

Main Methods:

  • Analysis of 95 surgically resected SCLC samples using immunohistochemical staining.
  • Correlation analysis between DLL3/ASCL1 expression and patient clinicopathological features.

Main Results:

  • DLL3 expression was detected in 83% of samples, with high expression in 47%.
  • ASCL1 expression was observed in 64% of samples.
  • A positive correlation was found between DLL3 and ASCL1 expression; neither was associated with survival, but DLL3 was more prevalent in advanced disease.

Conclusions:

  • DLL3 and ASCL1 are highly expressed in surgically resected SCLC.
  • DLL3 and ASCL1 represent potential therapeutic targets for SCLC, including early-stage disease and Rova-T treatment.

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