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

NPJ Precis Oncol. 2024 Nov 19;8(1):268. doi: 10.1038/s41698-024-00739-y.

Authors

Alejandra G Serrano^#¹, Pedro Rocha^#¹, Cibelle Freitas Lima¹, Allison Stewart², Bingnan Zhang², Lixia Diao³, Junya Fujimoto¹, Robert J Cardnell², Wei Lu¹, Khaja Khan¹, Beate Sable⁴, Aaron R Ellison⁴, Ignacio I Wistuba¹, Kyle F Concannon², Daniel M Halperin⁵, Czerniak Bogdan⁶, Kanishka Sircar⁶, Miao Zhang⁶, Kasey Cargill², Qi Wang³, Ana Aparicio⁷, Alexander Lazar⁶, Sharia Hernandez¹, Jeannelyn Estrella⁶, Preetha Ramalingam⁶, Adel El-Naggar⁶, Neda Kalhor⁶, Carl M Gay², Lauren Averett Byers^#⁸, Luisa M Solis Soto^#⁹

Affiliations

¹ Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
² Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
³ Department of Bioinformatics & Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁴ Amgen Inc., Thousand Oaks, CA, USA.
⁵ Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁶ Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁷ Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁸ Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. lbyers@mdanderson.org.
⁹ Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. lmsolis@mdanderson.org.

^# Contributed equally.

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.

Abstract

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