Lenvatinib, an angiogenesis inhibitor targeting VEGFR/FGFR, shows broad antitumor activity in human tumor xenograft models associated with microvessel density and pericyte coverage.

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Lenvatinib is an oral inhibitor of multiple receptor tyrosine kinases (RTKs) targeting vascular endothelial growth factor receptor (VEGFR1-3), fibroblast growth factor receptor (FGFR1-4), platelet growth factor receptor α (PDGFR α), RET and KIT. Antiangiogenesis activity of lenvatinib in VEGF- and FGF-driven angiogenesis models in both in vitro and in vivo was determined. Roles of tumor vasculature (microvessel density (MVD) and pericyte coverage) as biomarkers for lenvatinib were also examined in this study.

Related collections

Most cited references 24

Record: found
Abstract: found
Article: not found

Targeting the tumour vasculature: insights from physiological angiogenesis.

Alicia S Chung, John Lee, Napoleone Ferrara (2010)

The cardiovascular system ensures the delivery of nutrients, oxygen, and blood and immune cells to all organs and tissues: it is also responsible for the removal of waste metabolites. The vascular system develops and matures through two tightly regulated processes: vasculogenesis and angiogenesis. Angiogenesis is active only under specific physiological conditions in healthy adults but the vasculature can be aberrantly activated to generate new blood vessels during pathological conditions such as cancer and chronic inflammation. In this Opinion article we discuss the parallels and differences in the angiogenic process under either a physiological or a pathological state, especially tumorigenesis.

0 comments Cited 240 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Vascular endothelial growth factor regulates endothelial cell survival through the phosphatidylinositol 3'-kinase/Akt signal transduction pathway. Requirement for Flk-1/KDR activation.

H P Gerber, A E McMurtrey, J. Kowalski … (1998)

Vascular endothelial growth factor (VEGF) has been found to have various functions on endothelial cells, the most prominent of which is the induction of proliferation and differentiation. In this report we demonstrate that VEGF or a mutant, selectively binding to the Flk-1/KDR receptor, displayed high levels of survival activity, whereas Flt-1-specific ligands failed to promote survival of serum-starved primary human endothelial cells. This activity was blocked by the phosphatidylinositol 3'-kinase (PI3-kinase)-specific inhibitors wortmannin and LY294002. Endothelial cells cultured in the presence of VEGF and the Flk-1/KDR-selective VEGF mutant induced phosphorylation of the serine-threonine kinase Akt in a PI3-kinase-dependent manner. Akt activation was not detected in response to stimulation with placenta growth factor or an Flt-1-selective VEGF mutant. Furthermore, a constitutively active Akt was sufficient to promote survival of serum-starved endothelial cells in transient transfection experiments. In contrast, overexpression of a dominant-negative form of Akt blocked the survival effect of VEGF. These findings identify the Flk-1/KDR receptor and the PI3-kinase/Akt signal transduction pathway as crucial elements in the processes leading to endothelial cell survival induced by VEGF. Inhibition of apoptosis may represent a major aspect of the regulatory activity of VEGF on the vascular endothelium.

0 comments Cited 236 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Multi-kinase inhibitor E7080 suppresses lymph node and lung metastases of human mammary breast tumor MDA-MB-231 via inhibition of vascular endothelial growth factor-receptor (VEGF-R) 2 and VEGF-R3 kinase.

Toshimitsu Uenaka, Makoto Asada, Yasuhiro Funahashi … (2008)

Vascular endothelial growth factor (VEGF)-C/VEGF-receptor 3 (VEGF-R3) signal plays a significant role in lymphangiogenesis and tumor metastasis based on its effects on lymphatic vessels. However, little is known about the effect of inhibiting VEGF-R3 on lymphangiogenesis and lymph node metastases using a small-molecule kinase inhibitor. We evaluated the effect of E7080, a potent inhibitor of both VEGF-R2 and VEGF-R3 kinase, and bevacizumab on lymphangiogenesis and angiogenesis in a mammary fat pad xenograft model of human breast cancer using MDA-MB-231 cells that express excessive amounts of VEGF-C. Lymphangiogenesis was determined by lymphatic vessel density (LVD) and angiogenesis by microvessel density (MVD). In contrast to MDA-MB-435 cells, which expressed a similar amount of VEGF to MDA-MB-231 cells with an undetectable amount of VEGF-C, only MDA-MB-231 exhibited lymphangiogenesis in the primary tumor. E7080 but not bevacizumab significantly decreased LVD within the MDA-MB-231 tumor. E7080 and bevacizumab decreased MVD in both the MDA-MB-231 and MDA-MB-435 models. E7080 significantly suppressed regional lymph nodes and distant lung metastases of MDA-MB-231, whereas bevacizumab significantly inhibited only lung metastases. E7080 also decreased both MVD and LVD within the metastatic nodules at lymph nodes after resection of the primary tumor. Inhibition of VEGF-R3 kinase with E7080 effectively decreased LVD within MDA-MB-231 tumors, which express VEGF-C. Simultaneous inhibition of both VEGF-R2 and VEGF-R3 kinases by E7080 may be a promising new strategy to control regional lymph node and distant lung metastases.

0 comments Cited 174 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (iso-abbrev):

Title: Vascular cell

Publisher: Springer Science and Business Media LLC

ISSN: 2045-824X

ISSN (Print): 2045-824X

Publication date (Electronic): 2014

Volume: 6

Affiliations

[1 ] Oncology Product Creation Unit, Eisai Product Creation Systems, Eisai Co., Ltd., 5-1-3 Tokodai, Tsukuba, Ibaraki 300-2635, Japan.

[2 ] Biomarkers and Personalized Medicine Core Function Unit, Eisai Product Creation Systems, Eisai Co., Ltd., 5-1-3 Tokodai, Tsukuba, Ibaraki 300-2635, Japan.

[3 ] Biomarkers and Personalized Medicine Core Function Unit, Eisai Product Creation Systems, Eisai Inc., 4 Corporate Drive, Andover, MA 01810, U.S.A.

Article

Publisher Item ID: 2045-824X-6-18

DOI: 10.1186/2045-824X-6-18

PMC ID: 4156793

PubMed ID: 25197551

SO-VID: fce02ec2-7c43-4f3b-8307-81b31308d1e9

History

Keywords: FGFR kinase inhibitor,Lenvatinib,Microvessel density,Pericyte coverage,VEGFR2 kinase inhibitor

Data availability:

Keywords: FGFR kinase inhibitor, Lenvatinib, Microvessel density, Pericyte coverage, VEGFR2 kinase inhibitor

Lenvatinib, an angiogenesis inhibitor targeting VEGFR/FGFR, shows broad antitumor activity in human tumor xenograft models associated with microvessel density and pericyte coverage.

Read this article at

Abstract

Related collections

Fandom activity

Most cited references 24

Targeting the tumour vasculature: insights from physiological angiogenesis.

Vascular endothelial growth factor regulates endothelial cell survival through the phosphatidylinositol 3'-kinase/Akt signal transduction pathway. Requirement for Flk-1/KDR activation.

Multi-kinase inhibitor E7080 suppresses lymph node and lung metastases of human mammary breast tumor MDA-MB-231 via inhibition of vascular endothelial growth factor-receptor (VEGF-R) 2 and VEGF-R3 kinase.

Author and article information

Journal

Affiliations

Article

History

Comments

Comment on this article

Similar content 63

Cited by 180

Most referenced authors 1,677