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Cell Aggregation Assays to Evaluate the Binding of the Drosophila Notch with Trans-Ligands and its Inhibition by Cis-Ligands
Published on: January 2, 2018
Delta-like canonical Notch ligand 3 as a potential therapeutic target in malignancies: A brief overview
Kentaro Matsuo1, Kohei Taniguchi1,2, Hiroki Hamamoto1
1Department of General and Gastroenterological Surgery, Osaka Medical and Pharmaceutical University, Takatsuki, Japan.
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.
Insights
Delta-like canonical Notch ligand 3 (DLL3) is crucial in cell processes and linked to skeletal issues. Research explores DLL3
Area of Science:
- Molecular Biology
- Developmental Biology
- Oncology
Background:
- Delta-like canonical Notch ligand 3 (DLL3) is a key Notch pathway component involved in cellular differentiation and survival.
- DLL3 mutations cause skeletal abnormalities, and its expression is noted in neuroendocrine lung carcinoma.
- Targeting DLL3 with antibody-drug conjugates like rovalpituzumab tesirine (ROVA-T) showed initial promise but faced development setbacks.
Purpose of the Study:
- To review the multifaceted roles of DLL3 in various malignancies.
- To discuss the potential of DLL3 as a therapeutic target in cancer.
- To explore future research directions for DLL3-targeted therapies.
Main Methods:
- Literature review of studies on DLL3 function and expression in malignancies.
- Analysis of clinical trial data regarding DLL3-targeting agents.
- Synthesis of current understanding of DLL3's role in cancer biology.
Main Results:
- DLL3 is implicated in the pathogenesis of several cancers beyond lung neuroendocrine carcinoma.
- Despite ROVA-T's suspension, DLL3 remains a target of interest due to its expression patterns.
- Ongoing research aims to elucidate DLL3's precise mechanisms in cancer to enable new therapeutic strategies.
Conclusions:
- DLL3 presents a complex role in cancer, necessitating further investigation.
- Developing effective DLL3-targeted therapies requires a deeper understanding of its function in diverse malignancies.
- Future research holds promise for novel DLL3-based cancer treatments.
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