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Delta-like ligand 3 (DLL3) landscape in pulmonary and extra-pulmonary neuroendocrine neoplasms
Alejandra G Serrano1, Pedro Rocha1, Cibelle Freitas Lima1
1Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Abstract:
Delta-like Ligand 3 (DLL3) targeting therapies are promising in small cell lung cancer (SCLC) treatment. However, DLL3 expression in SCLC and other neuroendocrine neoplasms (NEN) is heterogeneous and not well characterized. We describe the landscape of DLL3 at the mRNA and protein levels across SCLC, large cell neuroendocrine carcinoma (LCNEC), and non-small cell lung cancer. Additionally, we explore its expression in extra-pulmonary NEN (EP-NEN) using a standardized DLL3 IHC assay. DLL3 expression is enriched in SCLC, LCNEC along with combined histology lung cancers. Moreover, we find a wide range of DLL3 expression in high-grade EP-NEN. We describe heterogenous DLL3 expression not only in SCLC but also in different NEN types. This comprehensive characterization of DLL3 can help guide future clinical trial design targeting DLL3 in NEN including LCNEC and EP-NEN that are lacking standard of care treatment options.
Insights
Delta-like Ligand 3 (DLL3) therapies show promise for neuroendocrine neoplasms (NEN). This study characterizes DLL3 expression across lung and extra-pulmonary NEN, revealing heterogeneity that can guide targeted therapy clinical trials.
Area of Science:
- Oncology
- Molecular Biology
- Translational Research
Background:
- Delta-like Ligand 3 (DLL3) is a therapeutic target in small cell lung cancer (SCLC).
- DLL3 expression patterns in SCLC and other neuroendocrine neoplasms (NEN) are not fully understood.
- Heterogeneity in DLL3 expression may impact treatment efficacy.
Purpose of the Study:
- To comprehensively characterize DLL3 expression at mRNA and protein levels across various NEN types.
- To evaluate DLL3 expression in SCLC, large cell neuroendocrine carcinoma (LCNEC), non-small cell lung cancer, and extra-pulmonary NEN (EP-NEN).
- To inform the design of future clinical trials targeting DLL3 in NEN.
Main Methods:
- Analysis of DLL3 mRNA and protein expression.
- Utilized a standardized DLL3 immunohistochemistry (IHC) assay.
- Evaluated expression across SCLC, LCNEC, non-small cell lung cancer, and EP-NEN.
Main Results:
- DLL3 expression is notably enriched in SCLC and LCNEC.
- A wide and heterogeneous range of DLL3 expression was observed in high-grade EP-NEN.
- Heterogeneity of DLL3 expression was confirmed across different NEN subtypes.
Conclusions:
- DLL3 expression is variable across SCLC, LCNEC, and EP-NEN.
- This characterization provides crucial data for developing DLL3-targeted therapies.
- Findings support the exploration of DLL3-targeted treatments in LCNEC and EP-NEN, which often lack standard care options.
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