Landscape of Delta-like-ligand 3 (DLL3) Expression Across Neuroendocrine Neoplasms (NENs)

Authors:

Anthony Crymes1, Mark G. Evans2, Andrew Elliott2, John R. Lozada3,4, Elisabeth I. Heath5, Benedito A. Carneiro6, Emil Lou3, Heloisa P. Soares7, Emmanuel S. Antonarakis3, Charles Ryan3, Chadi Nabhan2, Jennifer Marks1, Himisha Beltran8, Justin H. Hwang3

Background

  • Delta like ligand 3 (DLL3) is a cell surface protein and emerging therapeutic target in neuroendocrine carcinomas.
  • The clinical and molecular features associated with DLL3 expression across cancer types are not well defined.
  • Recent studies indicate that ~77% of neuroendocrine prostate cancers (NEPC) overexpress DLL3, as compared to metastatic castration resistant prostate cancers of the adenocarcinoma subtype (12.5%) or localized prostate tumor or prostate tissue (<1%).
  • Similarly in small cell lung cancer (SCLC) and other neuroendocrine carcinomas, DLL3 is highly expressed and an emerging target.
  • There are several ongoing clinical trials of drugs targeting DLL3 in neuroendocrine carcinomas, including T cell engagers and BiTEtherapies.
  • Defining the genomic landscape and aberrant signaling activity in DLL3-overexpressing neuroendocrine carcinomas will help elucidate regulators of DLL3 expression and may help improve patient selection for DLL3-targeted drugs.
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