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Open research questions in Angiogenesis and VEGF in Cancer

130 gap statements mined from Angiogenesis and VEGF in Cancer papers in our 4.5M-paper local library, which holds 639 papers on the topic — drawn mostly from each paper's own stated research gap, future-work, challenge and limitation notes, and its abstract. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one.

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What the literature leaves open

  • These findings support the possibility that EPC-OCNs may be involved in post-procedural osteogenic remodeling, although the biological and clinical significance of this observation remains uncertain.

    Dynamic Changes in Circulating Osteogenic Progenitor Cells Following TAVI: Implications for Vascular Remodeling—EPC and EPC-OCN Dynamics After TAVI · 2026 · DOI

  • In patients undergoing TAVI, EPC-OCN levels increased over time, whereas classical EPC levels remained stable, suggesting distinct biological responses among endothelial progenitor cell subpopulations after valve intervention. Translational Outlook: Larger studies are needed to determine whether EPC-OCN dynamics are associated with post-procedural remodeling and clinical outcomes after TAVI.

    Dynamic Changes in Circulating Osteogenic Progenitor Cells Following TAVI: Implications for Vascular Remodeling—EPC and EPC-OCN Dynamics After TAVI · 2026 · 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 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 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

  • Finally, several limitations of this study should be acknowledged. Although genotype–phenotype correlations in HAE remain incompletely defined, several studies have reported associations between mutation classes, residual C1INH levels, and disease severity.

    Modeling Hereditary Angioedema With Personalized EPSC ‐Derived Hepatocytes: A CRISPR ‐Validated Platform for Mutation‐Specific Mechanisms and Therapeutic Innovation · 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

  • 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

  • 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

  • Research on RUNX1 in aortic diseases remains sparse compared to established its inflammatory and TGF-β pathways, consistency across VSMC subpopulations and disease stages unclear.

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

  • The role of EPAS1 in HemECs remains less well characterized. The mechanisms underlying IH development, as well as the precise modes of action of propranolol, remain incompletely understood.

    EPAS1 knockdown is associated with cell cycle and DNA replication programs and MYC/E2F-related signatures in hemangioma endothelial cells · 2026 · DOI

  • The processes underlying HHT2, involving a complex interplay of signaling pathways that collectively contribute to aberrant angiogenesis, remain incompletely characterized.

    Targeting stiffness-dependent YAP/TAZ restores angiogenesis dynamics impaired by ALK1 knockout in silico · 2026 · DOI

  • There are still several key knowledge gaps that warrant further investigation in the future.

    Mechano-regulation of tumor metastasis: from intravasation to extravasation · 2026 · DOI

  • Germline knockout of Tie2 is embryonically lethal, making it necessary to generate an inducible knockout model. There is a need to investigate the role of Tie2 in vascular development and stability.

    Endothelial-specific Tie2 knockout mouse model - Tie2fl/fl;Cdh5-creERT2(+/−): a potent tool for inducible Tie2 deletion in vasculature across multiple organs · 2026 · DOI

  • The role of non-IGF-dependent mechanisms, such as N6-methyladenosine (m6A) modification, in IGFBP5-regulated angiogenesis is not well understood. The mechanisms underlying IGFBP5-driven angiogenesis are not fully elucidated.

    METTL14-dependent N6-methyladenosine modification of FGF16 participates in IGFBP5 deficiency-enhanced angiogenesis · 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

  • Endothelial cell adhesion molecule (ESAM) is a multifunctional protein implicated in tumor progression; however, its role in insensitivity to anti-HER2 therapy remains poorly understood.

    ESAM reduces sensitivity to anti-HER2 therapy in HER2-positive breast cancer by activating the mTOR pathway · 2026 · DOI

  • The chick chorioallantoic membrane (CAM) is a well-established model for studying angiogenesis, tumor growth, tissue grafting, and therapeutic responses; however, conventional in ovo approaches are limited by a short experimental window, immune-related constraints, and restricted imaging accessibility.

    The chick embryo chorioallantoic membrane as an in vivo assay to study the skin in melanoma and other skin pathological conditions · 2026 · DOI

  • Although its effects on malignant cells have been extensively studied, its impact on the surrounding bone marrow (BM) microenvironment (BME) remains unexplored.

    Remodeling of the bone marrow vasculature induced by venetoclax and azacitidine damage · 2026 · DOI

  • However, RT + Anti-PD-1 often fails to be effective in some patients with CRC, because a subset of tumors exhibits limited responsiveness through mechanisms that remain poorly understood.

    C5aR1-positive PMN-MDSC-induced angiogenesis limits the efficacy of radiotherapy combined with Anti-PD-1 immunotherapy · 2026 · DOI

  • The findings consistently demonstrated that CTEC offered greater biological and clinical value than CTC, indicating that tumor‑derived endothelial components may represent an underrecognized but critical aspect of liquid biopsy in lung cancer.

    Clinical utility of circulating tumor‑derived endothelial cells in lung cancer detection and prognosis prediction · 2026 · DOI

  • MFS thoracic aortas have increased stiffness, but how visco‐elastic and microstructural abnormalities affect in vivo hemodynamics remains inconclusive.

    Increased Disarray of Extracellular Matrix Collagen‐I Fiber Network and Compromised Biomechanics in Aortae From Marfan‐Syndrome Mice Assessed Through Combined Opto‐Biomechatronics · 2026 · DOI

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

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

  • Future validation in additional patient-derived systems, - Examination of HIF-2α in IH using multiple patient samples, - Investigation of the role of HIF-2α in IH…

    EPAS1 knockdown is associated with cell cycle and DNA replication programs and MYC/E2F-related signatures in hemangioma endothelial cells · 2026 · DOI

Most-cited papers in Angiogenesis and VEGF in Cancer

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Open questions raised by papers listed on this page include: (1) The process of endothelial maturation after myocardial infarction is unclear (“Coronary endothelial cells undergo venous-enriched disrupted maturation…”, 2026); (2) The role of endothelial cells in modulating tumour progression and chemoresistance is not fully understood (“Tumour endothelial cell reprogramming orchestrates angiocrine signalling to…”, 2026); (3) The molecular mechanisms underlying endothelial mechanotransduction are not fully understood (“Endothelial Mechanotransduction: Integrating Hemodynamic Forces, Molecular…”, 2026); (4) The molecular mechanisms underlying the link between insulin resistance and vascular inflammation in type 2 diabetes and coronary artery disease are not fully understood (“Orosomucoid 2 (ORM2) in type 2 diabetes and coronary artery disease: a…”, 2026); (5) The mechanisms underlying IH development, as well as the precise modes of action of propranolol, remain incompletely understood (“EPAS1 knockdown is associated with cell cycle and DNA replication programs and…”, 2026). 130 gap statements have been mined from Angiogenesis and VEGF in Cancer papers in our 4.5M-paper local library, which holds 639 papers on the topic; the gaps come from whichever of those papers state one. They are mostly the research gaps the authors state and the papers' abstracts, plus future-work, limitations and challenges passages. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one, so you can read the original claim in context.

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