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.