Emerging therapies targeting the delta-like ligand 3 (DLL3) in small cell lung cancer
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Authors
Rudin, C. M.Reck, M.
Johnson, M. L.
Blackhall, Fiona H
Hann, C. L.
Yang, J. C.
Bailis, J. M.
Bebb, G.
Goldrick, A.
Umejiego, J.
Paz-Ares, L.
Affiliation
Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USAIssue Date
2023
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Small cell lung cancer (SCLC) is an aggressive neuroendocrine carcinoma with a poor prognosis. Initial responses to standard-of-care chemo-immunotherapy are, unfortunately, followed by rapid disease recurrence in most patients. Current treatment options are limited, with no therapies specifically approved as third-line or beyond. Delta-like ligand 3 (DLL3), a Notch inhibitory ligand, is an attractive therapeutic target because it is overexpressed on the surface of SCLC cells with minimal to no expression on normal cells. Several DLL3-targeted therapies are being developed for the treatment of SCLC and other neuroendocrine carcinomas, including antibody-drug conjugates (ADCs), T-cell engager (TCE) molecules, and chimeric antigen receptor (CAR) therapies. First, we discuss the clinical experience with rovalpituzumab tesirine (Rova-T), a DLL3-targeting ADC, the development of which was halted due to a lack of efficacy in phase 3 studies, with a view to understanding the lessons that can be garnered for the rapidly evolving therapeutic landscape in SCLC. We then review preclinical and clinical data for several DLL3-targeting agents that are currently in development, including the TCE molecules-tarlatamab (formerly known as AMG 757), BI 764532, and HPN328-and the CAR T-cell therapy AMG 119. We conclude with a discussion of the future challenges and opportunities for DLL3-targeting therapies, including the utility of DLL3 as a biomarker for patient selection and disease progression, and the potential of rational combinatorial approaches that can enhance efficacy.Citation
Rudin CM, Reck M, Johnson ML, Blackhall F, Hann CL, Yang JC, et al. Emerging therapies targeting the delta-like ligand 3 (DLL3) in small cell lung cancer. J Hematol Oncol. 2023 Jun 24;16(1):66. PubMed PMID: 37355629. Pubmed Central PMCID: PMC10290806. Epub 2023/06/25. eng.Journal
Journal of Hematology and OncologyDOI
10.1186/s13045-023-01464-yPubMed ID
37355629Additional Links
https://dx.doi.org/10.1186/s13045-023-01464-yType
ArticleLanguage
enae974a485f413a2113503eed53cd6c53
10.1186/s13045-023-01464-y
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