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

doi:10.1038/s41698-024-00739-y

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 WangAna Aparicio, Alexander Lazar, Sharia Hernandez, Jeannelyn Estrella, Preetha Ramalingam, Adel El-Naggar, Neda Kalhor, Carl M. Gay, Lauren Averett Byers, Luisa M. Solis Soto

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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.

Original language	English (US)
Article number	268
Journal	npj Precision Oncology
Volume	8
Issue number	1
DOIs	https://doi.org/10.1038/s41698-024-00739-y
State	Published - Dec 2024

ASJC Scopus subject areas

Oncology
Cancer Research

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Serrano, A. G., Rocha, P., Freitas Lima, C., Stewart, A., Zhang, B., Diao, L., Fujimoto, J., Cardnell, R. J., Lu, W., Khan, K., Sable, B., Ellison, A. R., Wistuba, I. I., Concannon, K. F., Halperin, D. M., Bogdan, C., Sircar, K., Zhang, M., Cargill, K., ... Solis Soto, L. M. (2024). Delta-like ligand 3 (DLL3) landscape in pulmonary and extra-pulmonary neuroendocrine neoplasms. npj Precision Oncology, 8(1), Article 268. https://doi.org/10.1038/s41698-024-00739-y

Serrano, AG, Rocha, P, Freitas Lima, C, Stewart, A, Zhang, B , Diao, L, Fujimoto, J, Cardnell, RJ , Lu, W, Khan, K, Sable, B, Ellison, AR, Wistuba, II , Concannon, KF, Halperin, DM, Bogdan, C , Sircar, K , Zhang, M, Cargill, K, Wang, Q , Aparicio, A , Lazar, A , Hernandez, S , Estrella, J , Ramalingam, P , El-Naggar, A , Kalhor, N , Gay, CM , Byers, LA & Solis Soto, LM 2024, 'Delta-like ligand 3 (DLL3) landscape in pulmonary and extra-pulmonary neuroendocrine neoplasms', npj Precision Oncology, vol. 8, no. 1, 268. https://doi.org/10.1038/s41698-024-00739-y

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title = "Delta-like ligand 3 (DLL3) landscape in pulmonary and extra-pulmonary neuroendocrine neoplasms",

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.",

author = "Serrano, {Alejandra G.} and Pedro Rocha and {Freitas Lima}, Cibelle and Allison Stewart and Bingnan Zhang and Lixia Diao and Junya Fujimoto and Cardnell, {Robert J.} and Wei Lu and Khaja Khan and Beate Sable and Ellison, {Aaron R.} and Wistuba, {Ignacio I.} and Concannon, {Kyle F.} and Halperin, {Daniel M.} and Czerniak Bogdan and Kanishka Sircar and Miao Zhang and Kasey Cargill and Qi Wang and Ana Aparicio and Alexander Lazar and Sharia Hernandez and Jeannelyn Estrella and Preetha Ramalingam and Adel El-Naggar and Neda Kalhor and Gay, {Carl M.} and Byers, {Lauren Averett} and {Solis Soto}, {Luisa M.}",

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year = "2024",

month = dec,

doi = "10.1038/s41698-024-00739-y",

language = "English (US)",

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AU - Serrano, Alejandra G.

AU - Rocha, Pedro

AU - Freitas Lima, Cibelle

AU - Stewart, Allison

AU - Zhang, Bingnan

AU - Diao, Lixia

AU - Fujimoto, Junya

AU - Cardnell, Robert J.

AU - Lu, Wei

AU - Khan, Khaja

AU - Sable, Beate

AU - Ellison, Aaron R.

AU - Wistuba, Ignacio I.

AU - Concannon, Kyle F.

AU - Halperin, Daniel M.

AU - Bogdan, Czerniak

AU - Sircar, Kanishka

AU - Zhang, Miao

AU - Cargill, Kasey

AU - Wang, Qi

AU - Aparicio, Ana

AU - Lazar, Alexander

AU - Hernandez, Sharia

AU - Estrella, Jeannelyn

AU - Ramalingam, Preetha

AU - El-Naggar, Adel

AU - Kalhor, Neda

AU - Gay, Carl M.

AU - Byers, Lauren Averett

AU - Solis Soto, Luisa M.

PY - 2024/12

Y1 - 2024/12

N2 - 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.

AB - 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.

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ER -

Delta-like ligand 3 (DLL3) landscape in pulmonary and extra-pulmonary neuroendocrine neoplasms

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