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Dopamine D2 Receptor Agonists as Modulators of VEGF-A-Driven Angiogenesis: Mechanisms, Clinical Evidence, and Translational Opportunities

Published on Friday, 30 October 2026

Abstract

Angiogenesis mediated by vascular endothelial growth factor A (VEGF-A) is essential for physiological vascular remodeling but also drives pathological processes, including tumor growth, ocular neovascularization, and inflammation.

Emerging evidence has revealed that dopamine D2 receptor (DRD2) activation is a key inhibitory pathway that counterbalances VEGF-A-dependent endothelial activation and vascular permeability.

This review integrates current mechanistic insights into the effects of DRD2 agonists on endothelial signaling, focusing on their ability to suppress VEGF-A-induced proangiogenic signaling cascades.

Preclinical and translational studies have demonstrated that DRD2 agonists attenuate aberrant angiogenesis, promote vascular normalization, and mitigate VEGF-A-induced vascular leakage in diverse pathological contexts, including malignancy, ovarian hyperstimulation syndrome, endometriosis, and inflammatory lung injury.

Particular attention is given to the emerging model of tumor-derived VEGF-A inducing DRD2 expression within the tumor endothelium, establishing a reciprocal paracrine feedback loop with potential biomarker relevance.

Finally, the clinical safety profile and pharmacologic repositioning of DRD2 agonists are evaluated, and priorities for translational research are outlined to refine dosing, scheduling, and patient selection strategies in precision antiangiogenic therapy.

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About this publication.

- The Di Bella Method (A Fixed Part - Bromocriptine and/or Cabergoline);

- Prolactin inhibitors in oncology - In vitro, review and in vivo publications;

- The Di Bella Method (A Fixed Part - Somatostatin, Octreotide, Sandostatin LAR, analogues and/or derivatives since 1977);

- Somatostatin in oncology, the overlooked evidences - In vitro, review and in vivo publications;

- Publication, 2018 Jul: Over-Expression of GH/GHR in Breast Cancer and Oncosuppressor Role of Somatostatin as a Physiological Inhibitor (from Di Bella's Foundation);

- Publication, 2018 Sep: The over-expression of GH/GHR in tumour tissues with respect to healthy ones confirms its oncogenic role and the consequent oncosuppressor role of its physiological inhibitor, somatostatin: a review of the literature (from Di Bella's Foundation);

- Publication, 2019 Aug: The Entrapment of Somatostatin in a Lipid Formulation: Retarded Release and Free Radical Reactivity (from Di Bella's Foundation);

- Publication, 2019 Sep: Effects of Somatostatin and Vitamin C on the Fatty Acid Profile of Breast Cancer Cell Membranes (from Di Bella's Foundation);

- Publication, 2019 Sep: Effects of somatostatin, curcumin, and quercetin on the fatty acid profile of breast cancer cell membranes (from Di Bella's Foundation);

- Publication, 2020 Sep: Two neuroendocrine G protein-coupled receptor molecules, somatostatin and melatonin: Physiology of signal transduction and therapeutic perspectives (from Di Bella's Foundation);

The Di Bella's Method: Use of Prolactin Inhibitors Cabergoline and/or Bromocriptine, Somatostatin/Octreotide analogues and/or derivatives since 1977 associated with pseudo-Metronomic Chemotherapy Cyclophosphamide and/or Hydroxyurea - together with others chemical compounds: the dosage and administration schedule must be individualised for each patient - in several Oncological Pathologies:

- A retrospective observational clinical study of triple negative breast cancer cases treated with Di Bella Method: A preliminary data;

- The Synergism of Somatostatin, Melatonin, Vitamins Prolactin and Estrogen Inhibitors Increased Survival, Objective Response and Performance Status In 297 Cases of Breast Cancer;

- Complete objective response, stable for 5 years, with the Di Bella Method, of multiple-metastatic carcinoma of the breast;

- Evaluation of the safety and efficacy of the first-line treatment with somatostatin combined with melatonin, retinoids, vitamin D3, and low doses of cyclophosphamide in 20 cases of breast cancer: a preliminary report;

- The Di Bella Method (DBM) improved survival, objective response and performance status in a retrospective observational clinical study on 122 cases of breast cancer;

- Complete objective response to biological therapy of plurifocal breast carcinoma;

- A retrospective observational study on cases of anaplastic brain tumors treated with the Di Bella Method: A rationale and effectiveness;

- Recurrent Glioblastoma Multiforme (grade IV – WHO 2007): a case of complete objective response achieved by means of the concomitant administration of Somatostatin and Octreotide – Retinoids – Vitamin E – Vitamin D3 – Vitamin C – Melatonin – D2 R agonists (Di Bella Method – DBM) associated with Temozolomide;

- The Di Bella Method DBM improved survival objective response and performance status in a retrospective observational clinical study on 23 tumours of the head and neck;

- Chronic Lymphocytic Leukemia: Long-Lasting Remission with Combination of Cyclophosphamide, Somatostatin, Bromocriptine, Retinoids, Melatonin, and ACTH;

- Somatostatin, retinoids, melatonin, vitamin D, bromocriptine, and cyclophosphamide in advanced non-small-cell lung cancer patients with low performance status;

- Somatostatin, retinoids, melatonin, vitamin D, bromocriptine, and cyclophosphamide in chemotherapy-pretreated patients with advanced lung adenocarcinoma and low performance status;