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Open research questions in Angiogenesis and VEGF in Cancer

52 unresolved questions extracted from the limitations and future-work sections of 258 Angiogenesis and VEGF in Cancer papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • The role of S1P in osteosarcoma-associated angiogenesis is not fully understood - The contribution of tumor acidosis to this process is not well characterized

    Tumor-derived sphingosine-1-phosphate shapes angiogenesis in the acidic microenvironment of osteosarcoma via paracrine and autocrine signaling · 2026 · DOI

  • The development of novel therapeutic strategies for endothelial-related diseases is limited by the lack of understanding of the underlying mechanisms. The use of primary cells can bring forth variability from their donors, potentially affecting reproducibility in experiments. The study of endothelial cells in vitro is challenging due to the complex environment of endothelial cells in vivo.

    Investigating interactions between endothelial cells, type I interferon, and infection, highlighting a novel tonic IFN response enhanced by coculture with specific cell types · 2026 · DOI

  • The complex interplay between metabolism-related calcification and vascular calcification. The need to understand the underlying causes of vascular calcification. The development of effective treatment strategies for vascular calcification.

    Mechanisms of vascular calcification: cellular phenotype switching drives matrix remodeling and mineralized microenvironment formation · 2026 · DOI

  • Chronic inflammation and metabolic dysregulation are central drivers of atherosclerosis progression. The molecular mediators that connect impaired metabolic control to vascular injury remain incompletely defined. Direct evidence on ORM2 and pancreatic beta-cell function is not yet available in the published literature.

    Orosomucoid 2 (ORM2) in type 2 diabetes and coronary artery disease: a potential link between insulin resistance and vascular inflammation · 2026 · DOI

  • Targeting the tumor microenvironment and angiogenesis is an active area of research and development, as the angiogenic gene signatures in MCL remain poorly understood.

    Identifying the angiogenic receptor expression in mantle cell lymphoma patients and murine models · 2026 · DOI

  • Vascular smooth muscle cells are constantly subjected to cyclic stretch and hydrostatic pressure in vivo, yet the molecular responses to these stimuli remain incompletely understood.

    Distinct molecular profiles in human aortic smooth muscle cells under cyclic stretch and hydrostatic pressure · 2026 · DOI

  • Abstract Pathological choroidal neovascularization underlies vision loss in neovascular age-related macular degeneration (nAMD), yet the molecular regulators coordinating vascular and immune components remain incompletely defined.

    Lysosomal channel TPC2 modulates microglia-endothelial signaling in choroidal angiogenesis · 2026 · DOI

  • HHT patients inherit loss-of-function mutations affecting Alk1-Eng signaling; however, why this manifests as VMs remains poorly understood.

    A microphysiological system HHT-on-a-chip platform recapitulates patient vascular lesions · 2026 · DOI

  • Its role in flow‐dependent endothelial dysfunction and the upstream regulatory mechanisms remain incompletely understood.

    Phase Separation of TRIM21 Modulates PTPN14 Stability to Drive Flow‐Dependent Endothelial Activation and Atherogenesis · 2026 · DOI

  • ABSTRACT Local flow patterns determine the uneven distribution of atherosclerotic lesions, yet the underlying mechanism remains poorly defined.

    Phase Separation of TRIM21 Modulates PTPN14 Stability to Drive Flow‐Dependent Endothelial Activation and Atherogenesis · 2026 · DOI

  • Further study of the vascular permeability factor and its role in tumor ascites formation. Development of new therapies targeting the vascular permeability factor.

    Tumor Cells Secrete a Vascular Permeability Factor That Promotes Accumulation of Ascites Fluid · 1983 · DOI

  • The complexity of the angiogenic process. The difficulty in identifying specific factors that influence angiogenesis. The need for more sophisticated in vitro models to study angiogenesis.

    Training, What's It Worth?. · 1976 · DOI

  • The mechanism of tumor ascites formation is not well understood. The factor responsible for the increased influx of fluid in tumor growth is not identified.

    Tumor Cells Secrete a Vascular Permeability Factor That Promotes Accumulation of Ascites Fluid · 1983 · DOI

  • Given that SMC plasticity is a major limitation in supporting endothelial network formation, we systematically evaluated the effects of passage number, confluency, and freezing on primary SMC function.

    Immortalized smooth muscle cells enhance in vitro vasculogenesis · 2026 · DOI

  • The link between dermal mesenchymal stem cells and the angiopoietin 1/Tie2 axis in psoriasis remains unclear. The specific regulatory mechanisms underlying the imbalance between proangiogenic and antiangiogenic factors in psoriatic lesions remain to be fully elucidated.

    Dermal mesenchymal stem cells promote angiogenesis in HMEC-1 via activation of the angiopoietin 1/Tie2 pathway in psoriasis · 2026 · DOI

  • Our previous studies demonstrated that dermal mesenchymal stem cells (DMSCs) derived from psoriatic lesions can promote angiogenesis in human umbilical vein endothelial cells; however, the link between this proangiogenic effect and the Ang1/Tie2 axis remains unclear.

    Dermal mesenchymal stem cells promote angiogenesis in HMEC-1 via activation of the angiopoietin 1/Tie2 pathway in psoriasis · 2026 · DOI

  • The process of endothelial maturation after myocardial infarction is unclear. The factors driving pathological myocardial remodeling are not fully understood.

    Coronary endothelial cells undergo venous-enriched disrupted maturation following myocardial infarction · 2026 · DOI

  • The complex relationship between the endothelium and inflammation is not fully understood. The role of endothelial cells in regulating immune responses and inflammation is not well characterized. The development of novel therapeutic strategies for endothelial-related diseases is limited by the lack of understanding of the underlying mechanisms.

    Investigating interactions between endothelial cells, type I interferon, and infection, highlighting a novel tonic IFN response enhanced by coculture with specific cell types · 2026 · DOI

  • The current research often focuses on inflammation rather than immune-enabling vessels. There is a gap in understanding the relationship between endothelial epigenetic switching and vascular-readiness for cancer immunotherapy.

    From endothelial epigenetic switching to a vascular-readiness compass for cancer immunotherapy · 2026 · DOI

  • The study identifies a gap in the understanding of the underlying causes of vascular calcification. The review highlights the need for further research into the role of vascular smooth muscle cell phenotypic switching in vascular calcification.

    Mechanisms of vascular calcification: cellular phenotype switching drives matrix remodeling and mineralized microenvironment formation · 2026 · DOI

  • The role of endothelial cells in modulating tumour progression and chemoresistance is not fully understood. The mechanisms underlying adaptive resistance to Doxorubicin treatment are not well characterised.

    Tumour endothelial cell reprogramming orchestrates angiocrine signalling to drive chemoresistance in breast cancer · 2026 · DOI

  • The molecular mechanisms underlying endothelial mechanotransduction are not fully understood. A comprehensive understanding of the signalling architecture from initial force detection to functional outcomes and therapeutic opportunities is lacking.

    Endothelial Mechanotransduction: Integrating Hemodynamic Forces, Molecular Signalling, and Bioengineering Platforms for Cardiovascular Precision Medicine · 2026 · DOI

  • The molecular mechanisms underlying the link between insulin resistance and vascular inflammation in type 2 diabetes and coronary artery disease are not fully understood. The role of ORM2 in regulating hepatic lipid metabolism, insulin sensitivity, and immune regulation is not well characterized.

    Orosomucoid 2 (ORM2) in type 2 diabetes and coronary artery disease: a potential link between insulin resistance and vascular inflammation · 2026 · DOI

  • Further research into the molecular mechanisms underlying the signaling shift from the canonical Smad2/3 pathway toward TAK1-NF-κB signaling. Investigation into the potential therapeutic targets for aortic disease progression. Studies to understand the role of the perivascular microenvironment in the development of aortic dissection.

    The critical role of the RUNX1/NF-κB transcriptional complex–mediated PVAT–VSMC axis in aortic dissection · 2026 · DOI

  • The key transcriptional regulators linking microenvironmental alterations to VSMC phenotypic remodeling have yet to be clearly defined. The molecular determinants of the signaling shift from the canonical Smad2/3 pathway toward TAK1-NF-κB signaling remain incompletely understood.

    The critical role of the RUNX1/NF-κB transcriptional complex–mediated PVAT–VSMC axis in aortic dissection · 2026 · DOI

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52 open questions have been extracted from the limitations and future-work passages of 258 Angiogenesis and VEGF in Cancer papers in our library. Each one below links back to the study that raised it, so you can read the original claim in context.

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