Recent advances on anti-angiogenesis receptor tyrosine kinase inhibitors in cancer therapy

Qin, Shuang; Li, An‐Ping; Yi, Ming; Yu, Shengnan; Zhang, Mingsheng; Wu, Kongming

doi:10.1186/s13045-019-0718-5

Cited by 222 publications

(148 citation statements)

References 115 publications

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“…Other experimental approaches targeting MDSCs in the concept of cancer include the blockade of accumulation pathways like the CCL/CCR2 axis and IL-8/CXCR1/2 interactions, which may hinder the trafficking of MDSCs to the TME and inhibit extravasation [32]. Overall, current studies regarding anti-VEGF treatment are centered on the production of tyrosine kinase inhibitors in order to arrest the activation of VEGFR-mediated vascularization and other secondary angiogenic pathways using the same signaling transducers [89].…”

Section: Mdsc Targeting For Cancer Therapymentioning

confidence: 99%

Myeloid-Derived Suppressor Cells: Major Figures that Shape the Immunosuppressive and Angiogenic Network in Cancer

Vetsika

Koukos

Κotsakis

2019

Cells

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Myeloid-derived suppressor cells (MDSCs) constitute a vast population of immature myeloid cells implicated in various conditions. Most notably, their role in cancer is of great complexity. They exert immunosuppressive functions like hampering cancer immunity mediated by T lymphocytes and natural killer cells, while simultaneously they can recruit T regulatory cells to further promote immunosuppression, thus shielding tumor cells against the immune defenses. In addition, they were shown to support tumor invasion and metastasis by inducing vascularization. Yet again, in order to exert their angiogenic activities, they do have at their disposal a variety of occasionally overlapping mechanisms, mainly driven by VEGF/JAK/STAT signaling. In this concept, they have risen to be a rather attractive target for therapies, including depletion or maturation, so as to overcome cancer immunity and suppress angiogenic activity. Even though, many studies have been conducted to better understand these cells, there is much to be done yet. This article hopes to shed some light on the paradoxal complexity of these cells, while elucidating some of the key features of MDSCs in relation to immunosuppression and, most importantly, to the vascularization processes, along with current therapeutic options in cancer, in relation to MDSC depletion.

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Section: Mdsc Targeting For Cancer Therapymentioning

confidence: 99%

Myeloid-Derived Suppressor Cells: Major Figures that Shape the Immunosuppressive and Angiogenic Network in Cancer

Vetsika

Koukos

Κotsakis

2019

Cells

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“…One of these compensatory pathways is platelet-derived growth factor PDGF and PDGFR signaling which led to the development of new anti-angiogenic therapies in the treatment of cancer [60]. Additionally, c-Kit belongs to the group of tumor angiogenesis-promoting molecules and new tyrosine kinase receptor inhibitors have been developed which target also c-Kit [61]. As the Vascular endothelial growth factor (VEGF) pathway has been suggested already to be regulated by PPARβ/δ [7,46], we decided to investigate further a potential regulation of Pdgfrβ, Pdgfb, and c-kit.…”

Section: Rna Sequencing Further Certifies the Acquisition Of A Highlymentioning

confidence: 99%

Vascular PPARβ/δ Promotes Tumor Angiogenesis and Progression

Wagner

Martin

et al. 2019

Cells

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Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors, which function as transcription factors. Among them, PPARβ/δ is highly expressed in endothelial cells. Pharmacological activation with PPARβ/δ agonists had been shown to increase their angiogenic properties. PPARβ/δ has been suggested to be involved in the regulation of the angiogenic switch in tumor progression. However, until now, it is not clear to what extent the expression of PPARβ/δ in tumor endothelium influences tumor progression and metastasis formation. We addressed this question using transgenic mice with an inducible conditional vascular-specific overexpression of PPARβ/δ. Following specific over-expression of PPARβ/δ in endothelial cells, we induced syngenic tumors. We observed an enhanced tumor growth, a higher vessel density, and enhanced metastasis formation in the tumors of animals with vessel-specific overexpression of PPARβ/δ. In order to identify molecular downstream targets of PPARβ/δ in the tumor endothelium, we sorted endothelial cells from the tumors and performed RNA sequencing. We identified platelet-derived growth factor receptor beta (Pdgfrb), platelet-derived growth factor subunit B (Pdgfb), and the tyrosinkinase KIT (c-Kit) as new PPARβ/δ -dependent molecules. We show here that PPARβ/δ activation, regardless of its action on different cancer cell types, leads to a higher tumor vascularization which favors tumor growth and metastasis formation.

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Section: Classic Anti-angiogenic Therapiesmentioning

confidence: 99%

“…A number of anti-angiogenic drugs have been developed and proposed to limit tumor growth and expansion [34]. At present, the main anti-angiogenic therapies approved by the FDA are described in Table 2 [34]. The use of anti-angiogenic drugs in clinical practice, however, only showed an initial benefit in patients, followed by limited effectiveness and only a moderate disease-free survival [35].…”

Section: Classic Anti-angiogenic Therapiesmentioning

confidence: 99%

Alternative Strategies to Inhibit Tumor Vascularization

Brossa

Buono

Fallo

et al. 2019

IJMS

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Endothelial cells present in tumors show different origin, phenotype, and genotype with respect to the normal counterpart. Various mechanisms of intra-tumor vasculogenesis sustain the complexity of tumor vasculature, which can be further modified by signals deriving from the tumor microenvironment. As a result, resistance to anti-VEGF therapy and activation of compensatory pathways remain a challenge in the treatment of cancer patients, revealing the need to explore alternative strategies to the classical anti-angiogenic drugs. In this review, we will describe some alternative strategies to inhibit tumor vascularization, including targeting of antigens and signaling pathways overexpressed by tumor endothelial cells, the development of endothelial vaccinations, and the use of extracellular vesicles. In addition, anti-angiogenic drugs with normalizing effects on tumor vessels will be discussed. Finally, we will present the concept of endothelial demesenchymalization as an alternative approach to restore normal endothelial cell phenotype.

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Recent advances on anti-angiogenesis receptor tyrosine kinase inhibitors in cancer therapy

Cited by 222 publications

References 115 publications

Myeloid-Derived Suppressor Cells: Major Figures that Shape the Immunosuppressive and Angiogenic Network in Cancer

Myeloid-Derived Suppressor Cells: Major Figures that Shape the Immunosuppressive and Angiogenic Network in Cancer

Vascular PPARβ/δ Promotes Tumor Angiogenesis and Progression

Alternative Strategies to Inhibit Tumor Vascularization

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