Manipulating Angiogenesis by Targeting Endothelial Metabolism: Hitting the Engine Rather than the Drivers—A New Perspective?

Treps, Lucas; Conradi, Lena‐Christin; Harjes, Ulrike; Carmeliet, Peter

doi:10.1124/pr.116.012492

Cited by 46 publications

(41 citation statements)

References 188 publications

(210 reference statements)

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“…Glutamine is essential for redox homeostasis and biomass synthesis. In tumorigenesis, glutamine metabolism is up-regulated to compensate the energy requirement which was compromised due to reduced oxidative phosphor relation (OxPhos) flux [26,29,31,[35][36][37]. Hypoxia and acidic tumor environment turn "ON" the angiogenic switch.…”

Section: Tumor Ec Metabolism In Regulating Tumor Angiogenesismentioning

confidence: 99%

Anti-Angiogenic Effects of Phytochemicals on miRNA Regulating Breast Cancer Progression

et al. 2020

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Several phytochemicals have been identified for their role in modifying miRNA regulating tumor progression. miRNAs modulate the expression of several oncogenes and tumor suppressor genes including the genes that regulate tumor angiogenesis. Hypoxia inducible factor-1 alpha (HIF-1α) signaling is a central axis that activates oncogenic signaling and acts as a metabolic switch in endothelial cell (EC) driven tumor angiogenesis. Tumor angiogenesis driven by metabolic reprogramming of EC is crucial for tumor progression and metastasis in many different cancers, including breast cancers, and has been linked to aberrant miRNA expression profiles. In the current article, we identify different miRNAs that regulate tumor angiogenesis in the context of oncogenic signaling and metabolic reprogramming in ECs and review how selected phytochemicals could modulate miRNA levels to induce an anti-angiogenic action in breast cancer. Studies involving genistein, epigallocatechin gallate (EGCG) and resveratrol demonstrate the regulation of miRNA-21, miRNA-221/222 and miRNA-27, which are prognostic markers in triple negative breast cancers (TNBCs). Modulating the metabolic pathway is a novel strategy for controlling tumor angiogenesis and tumor growth. Cardamonin, curcumin and resveratrol exhibit their anti-angiogenic property by targeting the miRNAs that regulate EC metabolism. Here we suggest that using phytochemicals to target miRNAs, which in turn suppresses tumor angiogenesis, should have the potential to inhibit tumor growth, progression, invasion and metastasis and may be developed into an effective therapeutic strategy for the treatment of many different cancers where tumor angiogenesis plays a significant role in tumor growth and progression.

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Section: Tumor Ec Metabolism In Regulating Tumor Angiogenesismentioning

confidence: 99%

Anti-Angiogenic Effects of Phytochemicals on miRNA Regulating Breast Cancer Progression

et al. 2020

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“…Recently, Carmeliet and co-workers postulated the concept that EC metabolism represents the engine of ECs, onto which proangiogenic signals (such as VEGF) converge. 427 As a consequence, whereas tumors develop resistance to treatment directed at specific proangiogenic proteins, targeting metabolic pathways may block the activation of ECs that are exposed to multiple angiogenic mediators (see also Section 3.4). The potential of this novel approach has recently been illustrated in several elegant studies.…”

Section: 43mentioning

confidence: 99%

Tumor angiogenesis revisited: Regulators and clinical implications

Ronca

Benkheil

Mitola

et al. 2017

Medicinal Research Reviews

154

128

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“…This strategy is based on the postulate that EC metabolism is the engine onto which pro-angiogenic signals like VEGF and others converge and that ‘cooling down the overheated metabolism’ of ECs can paralyze angiogenic ECs and reduce pathological angiogenesis, regardless of how many angiogenic signals are still present upon neutralization of VEGF [3,75,76]. Since ECs are highly glycolytic [77], targeting glycolysis might provide an alternative new therapeutic opportunity for reducing pathological angiogenesis.…”

Section: Role Of Abnormal Vasculature In Tumor Progression and Therapmentioning

confidence: 99%

Vessel pruning or healing: endothelial metabolism as a novel target?

Cantelmo

Pircher

Kalucka

et al. 2017

Expert Opinion on Therapeutic Targets

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Introduction: Antiangiogenic drugs were originally designed to starve tumors by cutting off their vascular supply. Unfortunately, when these agents are used as monotherapy or in combination with chemotherapy, they provide only modest survival benefits in the order of weeks to months in most cancer patients. Strategies normalizing the disorganized tumor vasculature offer the potential to increase tumor perfusion and oxygenation, and to improve the efficacy of radio-, chemo- and immunotherapy, while reducing metastasis. Areas covered: This review discusses tumor vascular normalization (TVN) as an alternative strategy for anti-angiogenic cancer treatment. We summarize (pre)-clinical strategies that have been developed to normalize tumor vessels as well as their potential to enhance standard therapy. Notably, we describe how targeting endothelial cell metabolism offers new possibilities for antiangiogenic therapy through evoking TVN. Expert opinion: Several drugs targeting VEGF signaling are now clinically used for antiangiogenic cancer treatment. However, excessive blood vessel pruning impedes perfusion and causes tumor hypoxia, known to promote cancer cell dissemination and impair radio-, chemo- and immunotherapy. Normalized vessels lessen tumor hypoxia, impair cancer cell intravasation and enhance anticancer treatment. New data indicate that targeting endothelial cell metabolism is an alternative strategy of antiangiogenic cancer treatment via promotion of TVN.

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Manipulating Angiogenesis by Targeting Endothelial Metabolism: Hitting the Engine Rather than the Drivers—A New Perspective?

Cited by 46 publications

References 188 publications

Anti-Angiogenic Effects of Phytochemicals on miRNA Regulating Breast Cancer Progression

Anti-Angiogenic Effects of Phytochemicals on miRNA Regulating Breast Cancer Progression

Tumor angiogenesis revisited: Regulators and clinical implications

Vessel pruning or healing: endothelial metabolism as a novel target?

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