DLL3: an emerging target in small cell lung cancer
2019
Small cell lung cancer (SCLC) accounts for approximately 15% of all lung cancers. Despite high rates of response to first-line chemotherapy and radiotherapy, patients with
extensive-stagedisease eventually relapse, and very few patients survive more than 5 years from diagnosis. Treatment options for recurrent or refractory disease are limited, and the treatments that do exist are associated with significant treatment-related toxicities. Delta-like ligand 3 (DLL3) is an inhibitory Notch ligand that is highly expressed in SCLC and other
neuroendocrine tumorsbut minimally expressed in normal tissues. It is therefore being explored as a potential therapeutic target in SCLC. Here, we review the preclinical and clinical evidence for targeting DLL3 in SCLC and discuss several DLL3-specific therapies being developed for the treatment of SCLC: the
antibody-drug conjugate
rovalpituzumab tesirine, the bispecific T cell engager immuno-oncology therapy AMG 757, and the
chimeric antigen receptorT
cell therapyAMG 119.
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