Introduction: Neuroendocrine carcinomas are very aggressive tumors with few treatment options. DLL3 seems to be an optimal target for therapeutic intervention, as it is expressed mainly on the membrane of tumor cells with neuroendocrine origin.
Areas covered: In this article, we outline the preclinical and clinical studies published in the last years on DLL3 in neuroendocrine neoplasm, above all of lung origin. Furthermore, we review the current literature on the interaction between DLL3 and the tumor microenvironment.
Expert opinion: Several DLL3-targeting strategies have been proposed in the last years with mixed results. Understanding the influence of DLL3 on the tumor (immune) microenvironment and developing adoptive therapies directed against this optimal target might represent the key strategy. Building on the clinical data obtained so far, future trials on in vivo diagnostic tools for predictive purpose and new specific therapies are needed.
Keywords: DLL3; Notch pathway; adoptive cell therapies; immune therapy; neuroendocrine carcinomas; neuroendocrine tumors; tumor microenvironment.