Potential lymphangiogenesis therapies: Learning from current antiangiogenesis therapies—A review

Yamakawa, Michael; Doh, Susan; Santosa, Samuel M.; Montana, Mario; Qin, Ellen C.; Kong, Hyunjoon; Han, Kunsoo; Yu, Chwo‐Ming Joseph; Rosenblatt, Mark I.; Kazlauskas, Andrius; Chang, Jin Hong; Azar, Dimitri T.

doi:10.1002/med.21496

Cited by 43 publications

(47 citation statements)

References 224 publications

(401 reference statements)

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“…The potential benefits of anti-lymphangiogenic therapies for cancer treatment have been demonstrated in several pre-clinical cancer models, where blocking of VEGF-C and VEGF-D led to dramatic reduction in lymphatic vessel growth and metastasis formation (reviewed in Zheng et al, 2014). Moreover, several clinical studies targeting tyrosine kinase receptors including VEGFR1-3, FGFR, Tie2, C-MET and PDGFR-beta, that block both angiogenesis and lymphangiogenesis, reported increased survival of tumor bearing mice and human patients following treatment (reviewed in Duong et al, 2012;Dieterich and Detmar, 2016;Yamakawa et al, 2018).…”

Section: Therapies Targeting the Lymphatic Vasculature: Implicationsmentioning

confidence: 99%

Cellular Origins of the Lymphatic Endothelium: Implications for Cancer Lymphangiogenesis

Gutierrez-Miranda

Yaniv

2020

Front. Physiol.

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The lymphatic system plays important roles in physiological and pathological conditions. During cancer progression in particular, lymphangiogenesis can exert both positive and negative effects. While the formation of tumor associated lymphatic vessels correlates with metastatic dissemination, increased severity and poor patient prognosis, the presence of functional lymphatics is regarded as beneficial for anti-tumor immunity and cancer immunotherapy delivery. Therefore, a profound understanding of the cellular origins of tumor lymphatics and the molecular mechanisms controlling their formation is required in order to improve current strategies to control malignant spread. Data accumulated over the last decades have led to a controversy regarding the cellular sources of tumor-associated lymphatic vessels and the putative contribution of nonendothelial cells to this process. Although it is widely accepted that lymphatic endothelial cells (LECs) arise mainly from pre-existing lymphatic vessels, additional contribution from bone marrow-derived cells, myeloid precursors and terminally differentiated macrophages, has also been claimed. Here, we review recent findings describing new origins of LECs during embryonic development and discuss their relevance to cancer lymphangiogenesis.

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Section: Therapies Targeting the Lymphatic Vasculature: Implicationsmentioning

confidence: 99%

Cellular Origins of the Lymphatic Endothelium: Implications for Cancer Lymphangiogenesis

Gutierrez-Miranda

Yaniv

2020

Front. Physiol.

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“…The studies showed that VEGF-C plays important role in tumor metastasis. Therefore, VEGF-C and its receptor VEGFR-3 have been considered as the promising therapeutic target in cancer (Yamakawa et al, 2018). Intriguingly, VEGF-C was found a potential regulator for dietary regulation of adiposity and cholesterol metabolism because it is required for intestinal lymphatic vessel maintenance and fat absorption (Nurmi et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Prediction of VEGF-C as a Key Target of Pure Total Flavonoids From Citrus Against NAFLD in Mice via Network Pharmacology

Wang

et al. 2019

Front. Pharmacol.

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Pure total flavonoids from Citrus (PTFC) effectively reduce the symptoms of non-alcoholic fatty liver disease (NAFLD). Our previous microarray analysis uncovered the alterations of important signaling pathways in the treatment of NAFLD with PTFC. However, the underlying core genes that might be targeted by PTFC, which play important roles in the progression of NALFD are yet to be identified. In this study, we predicted the vascular endothelial growth factor-C (VEGF-C) as potential key molecular target of PTFC against NAFLD via network pharmacology analysis. The network pharmacology approach presented here provided important clues for understanding the mechanisms of PTFC treatment in the development of NAFLD.

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“…While there are currently no drugs approved which target lymphangiogenesis in cancer or other diseases, early animal studies are underway and human studies are eagerly anticipated. VEGF, epidermal growth factor receptor, fibroblast growth factor, and platelet‐derived growth factor pathways have been identified as potential targets . Similar to challenges encountered with cancer treatment, the problem with common pathways implicated in angiogenesis will need to be addressed and avoided.…”

Section: Important Considerations and Future Challengesmentioning

confidence: 99%

Granulomatous Inflammation in Tuberculosis and Sarcoidosis: Does the Lymphatic System Contribute to Disease?

2019

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A striking and unexplained feature of granulomatous inflammation is its anatomical association with the lymphatic system. Accumulating evidence suggests that lymphatic tracks and granulomas may alter the function of each other. The formation of new lymphatics, or lymphangiogenesis, is an adaptive response to tumor formation, infection, and wound healing. Granulomas also may induce lymphangiogenesis which, through a variety of mechanisms, could contribute to disease outcomes in tuberculosis and sarcoidosis. On the other hand, alterations in lymph node function and lymphatic draining may be primary events which attenuate the risk and severity of granulomatous inflammation. This review begins with an introduction of granulomatous inflammation and the lymphatic system. A role of the lymphatic system in tuberculosis and sarcoidosis is then hypothesized. With a focus on lymphangiogenesis in these diseases, and on the potential for this process to promote dissemination, parallels are established with the well-established role of lymphangiogenesis in tumor biology.

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Potential lymphangiogenesis therapies: Learning from current antiangiogenesis therapies—A review

Cited by 43 publications

References 224 publications

Cellular Origins of the Lymphatic Endothelium: Implications for Cancer Lymphangiogenesis

Cellular Origins of the Lymphatic Endothelium: Implications for Cancer Lymphangiogenesis

Prediction of VEGF-C as a Key Target of Pure Total Flavonoids From Citrus Against NAFLD in Mice via Network Pharmacology

Granulomatous Inflammation in Tuberculosis and Sarcoidosis: Does the Lymphatic System Contribute to Disease?

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