Targeting DLL3: Innovative Strategies for Tumor Treatment

Delta-like 3 (DLL3) is an oncogenic protein aberrantly expressed in several tumors, particularly in small-cell lung cancer. DLL3-targeted therapies have recently made significant progress, demonstrating promising preclinical and clinical efficacy. This review aims to explore the mechanisms, challeng...

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Main Authors: Hui Wang, Tong Zheng, Dan Xu, Chao Sun, Daqing Huang, Xiongxiong Liu
Format: Article
Language:English
Published: MDPI AG 2025-04-01
Series:Pharmaceutics
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Online Access:https://www.mdpi.com/1999-4923/17/4/520
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author Hui Wang
Tong Zheng
Dan Xu
Chao Sun
Daqing Huang
Xiongxiong Liu
author_facet Hui Wang
Tong Zheng
Dan Xu
Chao Sun
Daqing Huang
Xiongxiong Liu
author_sort Hui Wang
collection DOAJ
description Delta-like 3 (DLL3) is an oncogenic protein aberrantly expressed in several tumors, particularly in small-cell lung cancer. DLL3-targeted therapies have recently made significant progress, demonstrating promising preclinical and clinical efficacy. This review aims to explore the mechanisms, challenges, and future opportunities associated with therapies targeting DLL3 for cancer treatment. The biological characteristics of DLL3 and its role in the Notch signaling pathway are introduced first, delving into the role of DLL3 in tumorigenesis and cancer progression. Next, current therapeutic approaches targeting DLL3 are described, including antibody–drug conjugates, T cell engagers, chimeric antigen receptor T cells, and radiopharmaceutical therapy, highlighting their effectiveness and safety in clinical trials. Despite the promising prospects, difficulties remain in the use of DLL3 as a therapeutic target due to tumor heterogeneity, the development of resistance, potential adverse effects, and barriers to patient stratification. Therefore, the potential of combination therapies, the use of innovative drug delivery systems, and ongoing clinical trial advancements are also discussed. Finally, the potential of DLL3-targeted therapies is summarized, highlighting the importance of multidisciplinary research to guide the clinical application and optimization of this emerging treatment strategy. These approaches might provide new therapeutic options, potentially starting a new era in cancer treatment.
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spelling doaj-art-b84327258f0540f193dea3abc0d1ecc42025-08-20T02:18:10ZengMDPI AGPharmaceutics1999-49232025-04-0117452010.3390/pharmaceutics17040520Targeting DLL3: Innovative Strategies for Tumor TreatmentHui Wang0Tong Zheng1Dan Xu2Chao Sun3Daqing Huang4Xiongxiong Liu5Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, ChinaInstitute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, ChinaInstitute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, ChinaInstitute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, ChinaSchool of Nuclear Science and Engineering, East China University of Technology, Nanchang 330013, ChinaInstitute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, ChinaDelta-like 3 (DLL3) is an oncogenic protein aberrantly expressed in several tumors, particularly in small-cell lung cancer. DLL3-targeted therapies have recently made significant progress, demonstrating promising preclinical and clinical efficacy. This review aims to explore the mechanisms, challenges, and future opportunities associated with therapies targeting DLL3 for cancer treatment. The biological characteristics of DLL3 and its role in the Notch signaling pathway are introduced first, delving into the role of DLL3 in tumorigenesis and cancer progression. Next, current therapeutic approaches targeting DLL3 are described, including antibody–drug conjugates, T cell engagers, chimeric antigen receptor T cells, and radiopharmaceutical therapy, highlighting their effectiveness and safety in clinical trials. Despite the promising prospects, difficulties remain in the use of DLL3 as a therapeutic target due to tumor heterogeneity, the development of resistance, potential adverse effects, and barriers to patient stratification. Therefore, the potential of combination therapies, the use of innovative drug delivery systems, and ongoing clinical trial advancements are also discussed. Finally, the potential of DLL3-targeted therapies is summarized, highlighting the importance of multidisciplinary research to guide the clinical application and optimization of this emerging treatment strategy. These approaches might provide new therapeutic options, potentially starting a new era in cancer treatment.https://www.mdpi.com/1999-4923/17/4/520DLL3targeted therapysolid tumorclinical trials
spellingShingle Hui Wang
Tong Zheng
Dan Xu
Chao Sun
Daqing Huang
Xiongxiong Liu
Targeting DLL3: Innovative Strategies for Tumor Treatment
Pharmaceutics
DLL3
targeted therapy
solid tumor
clinical trials
title Targeting DLL3: Innovative Strategies for Tumor Treatment
title_full Targeting DLL3: Innovative Strategies for Tumor Treatment
title_fullStr Targeting DLL3: Innovative Strategies for Tumor Treatment
title_full_unstemmed Targeting DLL3: Innovative Strategies for Tumor Treatment
title_short Targeting DLL3: Innovative Strategies for Tumor Treatment
title_sort targeting dll3 innovative strategies for tumor treatment
topic DLL3
targeted therapy
solid tumor
clinical trials
url https://www.mdpi.com/1999-4923/17/4/520
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AT daqinghuang targetingdll3innovativestrategiesfortumortreatment
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