ArticleJCO precision oncology2025
Clinical and Pathologic Landscapes of Delta-Like Ligand 3 and Seizure-Related Homolog Protein 6 Expression in Neuroendocrine Carcinomas.
Article in JCO precision oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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Who cites it
1 citing paper in PubMed.
- What are the Unmet Needs in Managing Digestive Neuroendocrine Carcinomas?Current oncology reports · 2026Review
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Authors and funding
13 authors.
Funding
Abstract
purposeDelta-like ligand 3 (DLL3) and seizure-related homolog protein 6 (SEZ6) are appealing drug targets in neuroendocrine carcinomas (NECs) given their preferential expression on the tumor cell surface compared with normal cells. We aimed to describe the landscape of these proteins across NECs from eight different primary sites. PATIENTS AND
methodsWe used immunohistochemistry to assess 124 NEC tumor samples from any primary site for DLL3 and 53 for SEZ6 and defined positivity as ≥1% staining.
resultsDLL3 and SEZ6 were commonly expressed in our cohort (97 of 124, 78% and 43 of 53, 81% positivity rates, respectively) and frequently coexpressed when both tested (35 of 53, 66%). NECs of the breast, prostate, and GI system had the highest rates of DLL3 positivity (2 of 2, 100%; 15 of 16, 94%; and 14 of 17, 82%, respectively); all primary sites except lung exhibited 100% positivity rates for SEZ6. DLL3 expression and SEZ6 expression were seen in transformed NECs (12 of 17, 71% and 3 of 4, 75%, respectively) and in brain metastases (5 of 7, 71% and 1 of 2, 50%, respectively). Expression of both proteins tended to remain stable among 10 patients with serial biopsies. DLL3 expression did not affect progression-free survival (PFS) on first-line platinum/etoposide with or without immunotherapy among patients with metastatic lung NEC (median PFS 5.3
conclusionWe describe the landscape of DLL3 and SEZ6 coexpression across NECs, establishing a broad-based cohort of patients who might derive benefit from therapeutics in development targeting these cell surface determinants.
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