Delta‐like canonical Notch ligand 3 as a potential therapeutic target in malignancies: A brief overview

Abstract

Delta‐like canonical Notch ligand 3 (DLL3) is a member of the Delta/Serrate/Lag2 (DSL) Notch receptor ligand family and plays a crucial role in Notch signaling, which influences various cellular processes including differentiation, proliferation, survival, and apoptosis. DLL3 is expressed throughout the presomitic mesoderm and is localized to the rostral somatic compartments; mutations in DLL3 induce skeletal abnormalities such as spondylocostal dysostosis. Recently, DLL3 has attracted interest as a novel molecular target due to its high expression in neuroendocrine carcinoma of the lung. Moreover, a DLL3‐targeting Ab‐drug conjugate, rovalpituzumab tesirine (ROVA‐T), has been developed as a new treatment with proven antitumor activity. However, the development of ROVA‐T was suspended because of shorter overall survival compared to topotecan, the second‐line standard treatment. Thus, several studies on the mechanism and function of DLL3 in several malignancies are underway to find a new strategy for targeting DLL3. In this review, we discuss the roles of DLL3 in various malignancies and the future perspectives of DLL3‐related research, especially as a therapeutic target.

Semaphorin 6D as an independent predictor for better prognosis in clear cell renal cell carcinoma

“…4 E). The Notch signaling pathway is involved in various inflammatory diseases and cancers [ 16 , 17 ]. The KEGG pathway enrichment analysis showed that it was one of the most altered pathways.…”

Identification and Validation of a Prognostic Risk-Scoring Model Based on Ferroptosis-Associated Cluster in Acute Myeloid Leukemia

“…As a critical transcription factor involved in epithelial-mesenchymal transition, TWIST1 overexpression can enhance the susceptibility to chemotherapy drugs by promoting cell cycle entry and, thus, improve AML patients' outcomes (Chen et al, 2015;Wang et al, 2015). DLL3 was an atypical Notch ligand that has been investigated in many tumors as a therapeutic target (Matsuo et al, 2021). In AML, improved survival was observed in high expression of DLL3, and it may function by cell proliferation regulation (Yan et al, 2010;Takam Kamga et al, 2019).…”

Immunohistochemical analyses of the expression profiles of INSM1, ATRX, DAXX and DLL3 in solid papillary carcinomas of the breast

“…A previous study demonstrated that NOTCH 1 expression was absent in SPC ( 14 ), which corresponded to the fact that INSM1 is essential for neuroendocrine differentiation, and Notch 1 negatively regulates neuroendocrine differentiation ( 6 , 14 ). Moreover, DLL3 plays an important role and is considered an autonomous inhibitor of Notch signalling, and SPCs show positive immunoreactivity for Notch 2 and Notch 3 ( 14 , 20 ). DLL3 expression was not detected in all patients with SPC in the present cohort, consistent with the results of a previous study ( 23 ).…”

“…However, the frequency of loss of ATRX and DAXX expression and its prognostic significance in SPC patients has not yet been analysed. Moreover, δ-like canonical Notch ligand 3 (DLL3), which plays an important role in Notch signalling, is frequently expressed in neuroendocrine-related tumours, such as neuroendocrine carcinomas of the lungs ( 20 ). However, DLL-3 expression and its prognostic significance in SPC have not yet been analysed.…”