The Tumor Vessel Targeting Strategy: A Double-Edged Sword in Tumor Metastasis

Li, Xiaobo; Yong, Li; Lu, Weijin; Chen, Minfeng; Ye, Wen‐Cai; Zhang, Dongmei

doi:10.3390/cells8121602

Cited by 32 publications

(21 citation statements)

References 154 publications

(159 reference statements)

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“…Within the TME, the interplay between tumor vessels and pro-tumoral immune cells engages a vicious cycle that promotes tumor progression, where the hypoxic conditions within the lesion foster the evasion of tumor cells from immune surveillance, as well as promoting angiogenesis [ 8 ]. Importantly, tumor-associated vessels are strikingly abnormal and characterized by diffuse tortuosity, poor pericyte coverage and high permeability, providing favorable routes for metastatic dissemination [ 9 ]. For these reasons, the targeting of the tumor vasculature in combination with immune therapies represents an emerging strategy to improve the treatment of melanoma, as well as other malignancies [ 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

The Efficacy of Anti-PD-L1 Treatment in Melanoma Is Associated with the Expression of the ECM Molecule EMILIN2

Fejza

Polano

Camicia

et al. 2021

IJMS

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The use of immune checkpoint inhibitors has revolutionized the treatment of melanoma patients, leading to remarkable improvements in the cure. However, to ensure a safe and effective treatment, there is the need to develop markers to identify the patients that would most likely respond to the therapies. The microenvironment is gaining attention in this context, since it can regulate both the immunotherapy efficacyand angiogenesis, which is known to be affected by treatment. Here, we investigated the putative role of the ECM molecule EMILIN-2, a tumor suppressive and pro-angiogenic molecule. We verified that the EMILIN2 expression is variable among melanoma patients and is associated with the response to PD-L1 inhibitors. Consistently, in preclinical settings,the absence of EMILIN-2 is associated with higher PD-L1 expression and increased immunotherapy efficacy. We verified that EMILIN-2 modulates PD-L1 expression in melanoma cells through indirect immune-dependent mechanisms. Notably, upon PD-L1 blockage, Emilin2−/− mice displayed improved intra-tumoral vessel normalization and decreased tumor hypoxia. Finally, we provide evidence indicating that the inclusion of EMILIN2 in a number of gene expression signatures improves their predictive potential, a further indication that the analysis of this molecule may be key for the development of new markers to predict immunotherapy efficacy.

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Section: Introductionmentioning

confidence: 99%

The Efficacy of Anti-PD-L1 Treatment in Melanoma Is Associated with the Expression of the ECM Molecule EMILIN2

Fejza

Polano

Camicia

et al. 2021

IJMS

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“…Besides, a controversy has arisen concerning the application of therapies exclusively targeting blood vessels: the disruption of endothelial cell barrier caused by these agents might facilitate tumor cell extravasation. Moreover, the hypoxic condition induced by antiangiogenic treatments directly contributes to tumor cells EMT; metabolism shift; ECM invasion; and, paradoxically, may favor metastasis [303]. Conversely, the neutralization of VEGFR-1 specific ligands, i.e., VEGF-B and PlGF, and the selective blockade of VEGFR-1 activation, represents a promising strategy to specifically counteract tumor-associated angiogenesis as well as malignant processes not directly related to new blood vessels formation.…”

Section: Discussionmentioning

confidence: 99%

Role of VEGFs/VEGFR-1 Signaling and Its Inhibition in Modulating Tumor Invasion: Experimental Evidence in Different Metastatic Cancer Models

Ceci

Atzori

Lacal

et al. 2020

IJMS

175

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The vascular endothelial growth factor (VEGF) family members, VEGF-A, placenta growth factor (PlGF), and to a lesser extent VEGF-B, play an essential role in tumor-associated angiogenesis, tissue infiltration, and metastasis formation. Although VEGF-A can activate both VEGFR-1 and VEGFR-2 membrane receptors, PlGF and VEGF-B exclusively interact with VEGFR-1. Differently from VEGFR-2, which is involved both in physiological and pathological angiogenesis, in the adult VEGFR-1 is required only for pathological angiogenesis. Besides this role in tumor endothelium, ligand-mediated stimulation of VEGFR-1 expressed in tumor cells may directly induce cell chemotaxis and extracellular matrix invasion. Furthermore, VEGFR-1 activation in myeloid progenitors and tumor-associated macrophages favors cancer immune escape through the release of immunosuppressive cytokines. These properties have prompted a number of preclinical and clinical studies to analyze VEGFR-1 involvement in the metastatic process. The aim of the present review is to highlight the contribution of VEGFs/VEGFR-1 signaling in the progression of different tumor types and to provide an overview of the therapeutic approaches targeting VEGFR-1 currently under investigation.

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“…25 Tumor vascular targeting drugs provide a novel therapeutic strategy for cancer that is distinct from more commonly used treatments that exert direct cytotoxic effects on tumor cells. 26 VDAs are a new class of tumor vascular targeting drugs that are currently under clinical study. A total of 8 publications were included for metaanalysis to compare the efficacy of VDAs, VDAs combined with traditional therapy versus placebo, or placebo combined with traditional therapy, for the treatment of different tumor types.…”

Section: Discussionmentioning

confidence: 99%

Clinical Application of Tumor Vascular Disrupting Therapy: A Systematic Review and Meta-Analysis

Tsang

Gan

Zhang

et al. 2021

OTT

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The occurrence, progression, invasion and metastasis of tumors depend on a tumor vascular network. Vascular disrupting agents (VDAs) are a new class of drugs targeting the tumor vasculature, by blocking the existing tumor blood vessels. However, there is no clear consensus on the clinical efficacy of tumor vascular disrupting therapy. In this study, we performed the first systematic review and meta-analysis of published clinical trials focused on tumor vascular disrupting therapies. Materials and Methods: We searched PubMed, EMBASE, and the Cochrane Library to identify clinical trials that used VDAs to treat tumors. After literature screening and data extraction, according to inclusion and exclusion labels, meta-analysis was performed using RevMan5.3 software. Results: In this meta-analysis, we included 2659 patients from eight randomized controlled trials involving non-small-cell lung cancer, prostate, epithelial ovarian, fallopian tube, and primary peritoneal carcinoma. Compared with the control arm, the experimental arm exhibited an effective improvement of 0.5-year and 1-year survival, as well as the 6-month progression-free survival rate. There was no significant difference between patients in the experimental compared to the control arm with respect to objective response and disease control rates, and 12-month progression-free survival. Conclusion: Vascular disrupting therapy can effectively prolong the survival of cancer patients. However, for indicators of short-term efficacy, such as objective response rate and disease control rate, there is still a lack of high-quality, large-scale clinical trial data to confirm the effectiveness of VDAs.

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The Tumor Vessel Targeting Strategy: A Double-Edged Sword in Tumor Metastasis

Cited by 32 publications

References 154 publications

The Efficacy of Anti-PD-L1 Treatment in Melanoma Is Associated with the Expression of the ECM Molecule EMILIN2

The Efficacy of Anti-PD-L1 Treatment in Melanoma Is Associated with the Expression of the ECM Molecule EMILIN2

Role of VEGFs/VEGFR-1 Signaling and Its Inhibition in Modulating Tumor Invasion: Experimental Evidence in Different Metastatic Cancer Models

Clinical Application of Tumor Vascular Disrupting Therapy: A Systematic Review and Meta-Analysis

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