ArticleMolecular cancer therapeutics2016
Dll4 Inhibition plus Aflibercept Markedly Reduces Ovarian Tumor Growth.
Article in Molecular cancer therapeutics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 46 citations in OpenAlex.
- Emerging roles of Notch signaling in the tumor microenvironment of digestive system cancers.Frontiers in molecular biosciences · 2026Review
- The Role of Notch Signaling and Gut Microbiota in Autoinflammatory Diseases: Mechanisms and Future Views.Biomedicines · 2025Review
- Clinical Progresses and Challenges of Bispecific Antibodies for the Treatment of Solid Tumors.Molecular diagnosis & therapy · 2024Review
- Oncogenic Pathways and Targeted Therapies in Ovarian Cancer.Biomolecules · 2024Review
- Novel specific anti-ESM1 antibodies overcome tumor bevacizumab resistance by suppressing angiogenesis and metastasis.Cancer science · 2023Article
- Lymphatic vasculature in ovarian cancer.Biochimica et biophysica acta. Reviews on cancer · 2023Review
- Advances in understanding the role and mechanisms of tumor stem cells in HER2-positive breast cancer treatment resistance (Review).International journal of oncology · 2023Review
- Histone methyltransferase SETD1A interacts with notch and promotes notch transactivation to augment ovarian cancer development.BMC cancer · 2023Article
- "DEPHENCE" system-a novel regimen of therapy that is urgently needed in the high-grade serous ovarian cancer-a focus on anti-cancer stem cell and anti-tumor microenvironment targeted therapies.Frontiers in oncology · 2023Review
- NOTCH1 Intracellular Domain and the Tumor Microenvironment as Prognostic Markers in HNSCC.Cancers · 2022Article
- Heart failure and cancer: From active exposure to passive adaption.Frontiers in cardiovascular medicine · 2022Review
- Efficacy evaluation of multi-immunotherapy in ovarian cancer: From bench to bed.Frontiers in immunology · 2022Review
- Recent advances and challenges of bispecific antibodies in solid tumors.Experimental hematology & oncology · 2021Review
- Targeting Notch to Maximize Chemotherapeutic Benefits: Rationale, Advanced Strategies, and Future Perspectives.Cancers · 2021Review
- A CD10-OGP Membrane Peptolytic Signaling Axis in Fibroblasts Regulates Lipid Metabolism of Cancer Stem Cells via SCD1.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Article
- Theasaponin EMolecules (Basel, Switzerland) · 2021Article
- Targeting Notch in oncology: the path forward.Nature reviews. Drug discovery · 2021Review
- What is new about ovarian malignancies?Contemporary oncology (Poznan, Poland) · 2021Review
- Targeting the Notch Signaling Pathway in Chronic Inflammatory Diseases.Frontiers in immunology · 2021Review
- Notch signaling in female cancers: a multifaceted node to overcome drug resistance.Cancer drug resistance (Alhambra, Calif.) · 2021Review
Corrections and comments
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Authors and funding
17 authors at 2 institutions in 1 country.
Funding
Abstract
Delta-like ligand 4 (Dll4), one of the Notch ligands, is overexpressed in ovarian cancer, especially in tumors resistant to anti-VEGF therapy. Here, we examined the biologic effects of dual anti-Dll4 and anti-VEGF therapy in ovarian cancer models. Using Dll4-Fc blockade and anti-Dll4 antibodies (murine REGN1035 and human REGN421), we evaluated the biologic effects of Dll4 inhibition combined with aflibercept or chemotherapy in orthotopic mouse models of ovarian cancer. We also examined potential mechanisms by which dual Dll4 and VEGF targeting inhibit tumor growth using immunohistochemical staining for apoptosis and proliferation markers. Reverse-phase protein arrays were used to identify potential downstream targets of Dll4 blockade. Dual targeting of VEGF and Dll4 with murine REGN1035 showed superior antitumor effects in ovarian cancer models compared with either monotherapy. In the A2780 model, REGN1035 (targets murine Dll4) or REGN421 (targets human Dll4) reduced tumor weights by 62% and 82%, respectively; aflibercept alone reduced tumor weights by 90%. Greater therapeutic effects were observed for Dll4 blockade (REGN1035) combined with either aflibercept or docetaxel (P < 0.05 for the combination vs. aflibercept). The superior antitumor effects of REGN1035 and aflibercept were related to increased apoptosis in tumor cells compared with the monotherapy. We also found that GATA3 expression was significantly increased in tumor stroma from the mice treated with REGN1035 combined with docetaxel or aflibercept, suggesting an indirect effect of these combination treatments on the tumor stroma. These findings identify that dual targeting of Dll4 and VEGF is an attractive therapeutic approach. Mol Cancer Ther; 15(6); 1344-52. ©2016 AACR.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.