Angiogenesis in melanoma: an update with a focus on current targeted therapies

Jour, George; Ivan, Doina; Aung, Phyu P.

doi:10.1136/jclinpath-2015-203482

Cited by 59 publications

(58 citation statements)

References 127 publications

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“…Currently, clinical trials are evaluating whether antiangiogenic treatment in combination with immunotherapy or conventional chemotherapy can improve survival for patients with malignant melanoma [8]. The present study demonstrates that properdistatin treatment improves vascular function, suggesting that this treatment may increase the uptake of therapeutic drugs.…”

Section: Discussionmentioning

confidence: 58%

“…Several strategies have been developed to inhibit angiogenesis, including targeting of angiogenic stimulators or their receptors with monoclonal antibodies or tyrosine kinase inhibitors [4–6], and treatments with endogeneous angiogenic inhibitors or small peptides that mimic these inhibitors [7]. Some of these strategies have been evaluated in clinical trials, but none of the antiangiogenic treatments have been shown to improve survival for patients with malignant melanoma when used as monotherapy [8]. Currently the effect of antiangiogenic treatment in combination with conventional chemotherapy or immunotherapy is evaluated for patients with malignant melanoma [8].…”

Section: Introductionmentioning

confidence: 99%

“…Some of these strategies have been evaluated in clinical trials, but none of the antiangiogenic treatments have been shown to improve survival for patients with malignant melanoma when used as monotherapy [8]. Currently the effect of antiangiogenic treatment in combination with conventional chemotherapy or immunotherapy is evaluated for patients with malignant melanoma [8]. …”

Section: Introductionmentioning

confidence: 99%

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Properdistatin inhibits angiogenesis and improves vascular function in human melanoma xenografts with low thrombospondin-1 expression

et al. 2016

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In this study, the effect of properdistatin, a novel peptide derived from the thrombospondin 1 (TSP-1) domain of properdin, was investigated in three melanoma xenograft models with different TSP-1 expression. The tumors were grown in dorsal window chambers and were treated with 80 mg/kg/day properdistatin or vehicle. Morphological parameters of the tumor vasculature were assessed from high resolution transillumination images. Blood supply time (i.e., the time required for arterial blood to flow from a supplying artery to downstream microvessels) and plasma velocities were assessed from first-pass imaging movies recorded after a bolus of fluorescence-labeled dextran had been administered intravenously. Gene and protein expression of TSP-1 were assessed with quantitative PCR and immunohistochemistry, respectively. Properdistatin treatment inhibited angiogenesis in low TSP-1 expressing tumors but did not alter the vasculature in high TSP-1 expressing tumors. In low TSP-1 expressing tumors, properdistatin selectively removed small-diameter capillaries, but did not change the morphology of tumor arterioles or tumor venules. Properdistatin also reduced blood supply times and increased plasma velocities, implying that the treatment reduced the geometric resistance to blood flow and improved vascular function.

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Section: Discussionmentioning

confidence: 58%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Properdistatin inhibits angiogenesis and improves vascular function in human melanoma xenografts with low thrombospondin-1 expression

et al. 2016

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“…These include the use of endogenous angiogenic inhibitors or small peptides that mimic these inhibitors [2], and inhibition of angiogenic stimulators or their receptors by using monoclonal antibodies or tyrosine kinase inhibitors [3–5]. There is substantial evidence that melanoma progression requires angiogenesis [6, 7]. Accordingly, several antiangiogenic agents have been tested in clinical trials but none of the agents have improved survival for patients with malignant melanoma when used as a single treatment [7].…”

Section: Introductionmentioning

confidence: 99%

“…There is substantial evidence that melanoma progression requires angiogenesis [6, 7]. Accordingly, several antiangiogenic agents have been tested in clinical trials but none of the agents have improved survival for patients with malignant melanoma when used as a single treatment [7]. Currently, clinical trials are evaluating whether antiangiogenic treatment in combination with immunotherapy or conventional chemotherapy can improve survival for patients with malignant melanoma [7].…”

Section: Introductionmentioning

confidence: 99%

Antiangiogenic agents targeting different angiogenic pathways have opposite effects on tumor hypoxia in R-18 human melanoma xenografts

Gaustad¹,

Simonsen²,

Andersen³

et al. 2017

BMC Cancer

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BackgroundStudies comparing the effect of antiangiogenic agents targeting different angiogenic pathways are sparse. The purpose of this study was to compare the effect of properdistatin and sunitinib treatment in a preclinical model of malignant melanoma. Properdistatin is a small peptide derived from the thrombospondin-1 domain of the plasma protein properdin, and sunitinib is a tyrosine kinase inhibitor targeting several receptors including the vascular endothelial growth factor receptors.MethodsR-18 human melanoma xenografts growing in dorsal window chambers were treated with properdistatin, sunitinib, or vehicle. Parameters describing the morphology of tumor vasculature were assessed from high-resolution transillumination images, and BST (blood supply time; the time needed for arterial blood to flow from the main supplying artery to downstream microvessels) was assessed from first-pass imaging movies recorded after a bolus of fluorescence-labeled dextran had been administered intravenously. Tumor hypoxia was assessed from immunohistochemical preparations of the imaged tissue by using pimonidazole as a hypoxia marker.ResultsProperdistatin treatment selectively removed small-diameter vessels and reduced BST, whereas sunitinib treatment reduced the density of small- and large-diameter vessel similarly and did not change BST. These observations imply that properdistatin treatment reduced geometric resistance to blood flow and improved vascular function, whereas sunitinib treatment did not affect vascular function. Accordingly, sunitinib-treated tumors showed higher hypoxic fractions than properdistatin-treated tumors.ConclusionsProperdistatin and sunitinib both inhibited angiogenesis, but had distinctly different effects on vascular morphology, vascular function, and extent of hypoxia in R-18 human melanoma xenografts.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-017-3404-4) contains supplementary material, which is available to authorized users.

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Molecular insights into melanoma brain metastases

Westphal

Niessner

2017

Cancer

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Substantial proportions of patients with metastatic melanoma develop brain metastases during the course of their disease, often resulting in significant morbidity and death. Despite recent advances with BRAF/MEK and immune-checkpoint inhibitors in the treatment of patients who have melanoma with extracerebral metastases, patients who have melanoma brain metastases still have poor overall survival, highlighting the need for further therapy options. A deeper understanding of the molecular pathways involved in the development of melanoma brain metastases is required to develop more brain-specific therapies. Here, the authors summarize the currently known preclinical data and describe steps involved in the development of melanoma brain metastases. Only by knowing the molecular background is it possible to design new therapeutic agents that can be used to improve the outcome of patients with melanoma brain metastases.

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Angiogenesis in melanoma: an update with a focus on current targeted therapies

Cited by 59 publications

References 127 publications

Properdistatin inhibits angiogenesis and improves vascular function in human melanoma xenografts with low thrombospondin-1 expression

Properdistatin inhibits angiogenesis and improves vascular function in human melanoma xenografts with low thrombospondin-1 expression

Antiangiogenic agents targeting different angiogenic pathways have opposite effects on tumor hypoxia in R-18 human melanoma xenografts

Molecular insights into melanoma brain metastases

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