The Great Escape; the Hallmarks of Resistance to Antiangiogenic Therapy

Beijnum, Judy R. van; Nowak-Śliwińska, Patrycja; Huijbers, Elisabeth J. M.; Thijssen, Victor L.; Griffioen, Arjan W.

doi:10.1124/pr.114.010215

Cited by 190 publications

(182 citation statements)

References 240 publications

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“…Currently, the progress of tumor resistance to therapy is a huge challenge. According to the data presented in figure 4, there are many mechanisms responsible for tumor progression even though used anti-angiogenic therapy [53,83].…”

Section: Tumor Resistance To Anti-angiogenic Therapymentioning

confidence: 99%

“…Pro-angiogenic pathways, in which EGF, PDGF, bFGF, HGF, or IGF is involved, can be alternative to VEGF pathway [35]. It is worth noting that these agents can be produced not only by ECs, but also for example by CAFs [53,83]. Recently, ECs resistance as a result of VEGFR2 activity, without VEGF contribution was focused [17].…”

Section: Tumor Resistance To Anti-angiogenic Therapymentioning

confidence: 99%

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Tumor Blood Vessels and Vasculogenic Mimicry – Current Knowledge and Searching for New Cellular/Molecular Targets of Anti-Angiogenic Therapy

Knopik-Skrocka

Kręplewska

Jarmołowska-Jurczyszyn

2017

Advances in Cell Biology

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Summary: Blood vessel formation in tumor is defined as tumor angiogenesis. So far, the most known its mechanism is sprouting, which means formation of blood vessels from existing ones, as a result of the proliferation and migration of endothelial cells. The main mitogenic factor of these cells is vascular endothelial growth factor VEGF, acting by VEGFR-2 receptors. Recent studies have provided knowledge about the ability of tumors to form vessel-like structures. The phenomenon was called vascular mimicry. Tumor cells show a high plasticity and they can undergo differentiation to the ones with phenotype similar to endothelial cells. Each of the known tumor angiogenesis mechanisms is a result of many different factors and cell cooperation in tumor microenvironment. Tumor ability to the heterogeneous vascularization forces developing of complex, anti-angiogenic therapy directed to different molecular and cellular targets. Therapies, used so far, often lead to drug-induced hypoxia, which increases tumor cell aggressiveness and metastasis.Keywords: tumor angiogenesis, vasculogenic mimicry, anti-angiogenic strategies, resistance to anti-angiogenic therapy Sprouting angiogenesis -formation via endothelial cells proliferation and migration towards avascular tumor area of new branches of blood vessels Intussusception -formation of blood vessels as a result of intussusception (septum) inside existing blood vessels Co-option -oxygen and nutrients acquire as a result of tumor cells migration along existing blood vessels Vasculogenic mimicry -formation by tumor cells of vessel-like structures, without endothelial cells participation Vasculogenesis -formation of tumor blood vessels de novo, as a result of endothelial progenitor cells recruitment

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Section: Tumor Resistance To Anti-angiogenic Therapymentioning

confidence: 99%

Section: Tumor Resistance To Anti-angiogenic Therapymentioning

confidence: 99%

Tumor Blood Vessels and Vasculogenic Mimicry – Current Knowledge and Searching for New Cellular/Molecular Targets of Anti-Angiogenic Therapy

Knopik-Skrocka

Kręplewska

Jarmołowska-Jurczyszyn

2017

Advances in Cell Biology

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“…Resistance to antiangiogenic agents can develop, mainly through the activation of other pathways like fibroblast growth factor (FGF) and platelet derived growth factor (PDGF). [9] Some authors have argued that, since resistance is established, the sudden suspension of the antiangiogenic drug can rapidly increase blood vessels formation, with more pronounced angiogenesis and faster prog ression, sug gesting possible benefits from longer treatment durations. [10] Recently, two randomized trials investigated the administration of bevacizumab beyond progression.…”

Section: Introductionmentioning

confidence: 99%

Protracted inhibition of vascular endothelial growth factor signaling improves survival in metastatic colorectal cancer: A systematic review

Montagnani

Leonardo

Pino

et al. 2017

Journal of Translational Internal Medicine

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Clinical data suggest that beyond-progression, the blockade of angiogenesis is associated with improved survivals in colorectal cancer. We conducted a systematic review to investigate the therapeutic effects of antiangiogenic drugs administered as later lines of treatment in patients already progressed to a previous anti-VEGF based treatment. An extensive literature search was conducted. Hazard ratios (HR) for progression (PFS) and death (OS) were extracted. An inverse-variance meta-analysis model was implemented. 6 randomized controlled trials were retrieved, including 3407 patients, treated with different antiangiogenic drugs. All of them had progressed during or after a previous line of treatment with bevacizumab. Overall, both PFS (HR=0.63, P <0.001) and OS (HR=0.81 , P < 0.001) were significantly increased with the use of antiangiogenic drug. No heterogeneity was observed despite different drugs. Protracted inhibition of the VEGF pathway is associated with a significant improvement of both PFS and OS, independently from the antiangiogenic agent used.

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“…3 Also, due to an increase in the emergence of resistance to these agents, there is an enormous interest in researchers to develop novel angiogenesis inhibitors with efficient therapeutics. 4 Despite a large body of evidence pointing towards the antiangiogenic activity of zinc, the potential of zinc, as an angiogenesis inhibitor, remains unexplored. First, depletion of zinc has been reported to increase the expression of proangiogenic cytokines such as VEGF, interleukin 6 (IL-6), and IL-8 in prostate cancer cells.…”

Section: Introductionmentioning

confidence: 99%

Antiangiogenic activity of zinc and zinc-sorafenib combination using the chick chorioallantoic membrane assay: a descriptive study

Kumar¹,

Meshram²,

Rastogi³

et al. 2017

Int J Basic Clin Pharmacol

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Background: Zinc, a trace element, is known for downregulating several proangiogenic growth factors and cytokines. However, its antiangiogenic activity is not adequately studied. The present study was aimed to evaluate the possible antiangiogenic activity of zinc via the chick chorioallantoic membrane (CAM) assay. Also, the antiangiogenic activity of the combination therapy of zinc with various doses of sorafenib, a tyrosine kinase inhibitor, was evaluated.Methods: A pilot study was initially conducted so as to select suitable doses of zinc and sorafenib. The antiangiogenic activity after combining zinc 2.5 μg/embryo with sorafenib 1, and 2 μg/embryo was also evaluated. The antiangiogenic activity was quantified in terms of total length of blood vessels, number of junctions, number of branching points, and mean length of the blood vessels.Results: Zinc 2.5 μg/embryo showed significant (p <0.05) antiangiogenic activity, as compared to the control group. However, its effect was not comparable to that of sorafenib 2 μg/embryo. The combination of zinc 2.5 μg/embryo with sorafenib 2 μg/embryo did not show an additive/synergistic effect. The combination of zinc 2.5 μg/embryo with sorafenib 1 μg/embryo produced an antiangiogenic activity which was comparable (p >0.05) to that of sorafenib 2 μg/embryo.Conclusions: Zinc caused significant antiangiogenic activity in the CAM assay. The lack of addition/synergism in the zinc-sorafenib combination could have been due to the variability in the dose/ratio selection. Addition of zinc to sorafenib therapy could improve treatment tolerability, reduce cost of therapy, and reduce the emergence of drug resistance. Future mechanistic studies could identify the exact pharmacodynamics of zinc as an angiogenesis inhibitor.

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The Great Escape; the Hallmarks of Resistance to Antiangiogenic Therapy

Cited by 190 publications

References 240 publications

Tumor Blood Vessels and Vasculogenic Mimicry – Current Knowledge and Searching for New Cellular/Molecular Targets of Anti-Angiogenic Therapy

Tumor Blood Vessels and Vasculogenic Mimicry – Current Knowledge and Searching for New Cellular/Molecular Targets of Anti-Angiogenic Therapy

Protracted inhibition of vascular endothelial growth factor signaling improves survival in metastatic colorectal cancer: A systematic review

Antiangiogenic activity of zinc and zinc-sorafenib combination using the chick chorioallantoic membrane assay: a descriptive study

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