DLL3, or Delta-like ligand 3, is a protein that is overexpressed in a significant proportion of small cell lung cancer (SCLC) tumors. It is a type of ligand that interacts with the Notch signaling pathway, which is involved in cell differentiation and proliferation. DLL3 is considered an attractive target for cancer therapies because of its limited expression in normal tissues, which may reduce the risk of on-target, off-tumor toxicity. Therapeutic strategies targeting DLL3 include antibody-drug conjugates (ADCs), bispecific T-cell engagers (BiTEs), and chimeric antigen receptor (CAR) T-cell therapies. These approaches aim to direct immune cells to DLL3-expressing cancer cells, leading to their destruction. Notably, DLL3-targeted therapies are in various stages of clinical development, with some showing promise in early-phase trials for the treatment of SCLC, which has limited treatment options and a generally poor prognosis. The development of DLL3-targeted therapies represents a significant effort to improve outcomes for patients with this aggressive form of lung cancer.
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