npj Precision Oncology (Nov 2024)
Delta-like ligand 3 (DLL3) landscape in pulmonary and extra-pulmonary neuroendocrine neoplasms
- Alejandra G. Serrano,
- Pedro Rocha,
- Cibelle Freitas Lima,
- Allison Stewart,
- Bingnan Zhang,
- Lixia Diao,
- Junya Fujimoto,
- Robert J. Cardnell,
- Wei Lu,
- Khaja Khan,
- Beate Sable,
- Aaron R. Ellison,
- Ignacio I. Wistuba,
- Kyle F. Concannon,
- Daniel M. Halperin,
- Czerniak Bogdan,
- Kanishka Sircar,
- Miao Zhang,
- Kasey Cargill,
- Qi Wang,
- Ana Aparicio,
- Alexander Lazar,
- Sharia Hernandez,
- Jeannelyn Estrella,
- Preetha Ramalingam,
- Adel El-Naggar,
- Neda Kalhor,
- Carl M. Gay,
- Lauren Averett Byers,
- Luisa M. Solis Soto
Affiliations
- Alejandra G. Serrano
- Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center
- Pedro Rocha
- Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center
- Cibelle Freitas Lima
- Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center
- Allison Stewart
- Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center
- Bingnan Zhang
- Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center
- Lixia Diao
- Department of Bioinformatics & Computational Biology, The University of Texas MD Anderson Cancer Center
- Junya Fujimoto
- Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center
- Robert J. Cardnell
- Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center
- Wei Lu
- Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center
- Khaja Khan
- Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center
- Beate Sable
- Amgen Inc.
- Aaron R. Ellison
- Amgen Inc.
- Ignacio I. Wistuba
- Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center
- Kyle F. Concannon
- Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center
- Daniel M. Halperin
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center
- Czerniak Bogdan
- Department of Pathology, The University of Texas MD Anderson Cancer Center
- Kanishka Sircar
- Department of Pathology, The University of Texas MD Anderson Cancer Center
- Miao Zhang
- Department of Pathology, The University of Texas MD Anderson Cancer Center
- Kasey Cargill
- Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center
- Qi Wang
- Department of Bioinformatics & Computational Biology, The University of Texas MD Anderson Cancer Center
- Ana Aparicio
- Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center
- Alexander Lazar
- Department of Pathology, The University of Texas MD Anderson Cancer Center
- Sharia Hernandez
- Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center
- Jeannelyn Estrella
- Department of Pathology, The University of Texas MD Anderson Cancer Center
- Preetha Ramalingam
- Department of Pathology, The University of Texas MD Anderson Cancer Center
- Adel El-Naggar
- Department of Pathology, The University of Texas MD Anderson Cancer Center
- Neda Kalhor
- Department of Pathology, The University of Texas MD Anderson Cancer Center
- Carl M. Gay
- Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center
- Lauren Averett Byers
- Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center
- Luisa M. Solis Soto
- Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center
- DOI
- https://doi.org/10.1038/s41698-024-00739-y
- Journal volume & issue
-
Vol. 8,
no. 1
pp. 1 – 13
Abstract
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.
