Anti-angiogenic agents for the treatment of solid tumors: Potential pathways, therapy and current strategies – A review

Al‐Abd, Ahmed M.; Alamoudi, Abdulmohsin J.; Abdel-Naim, Ashraf B.; Neamatallah, Thikryat; Ashour, Osama M.

doi:10.1016/j.jare.2017.06.006

Cited by 157 publications

(125 citation statements)

References 195 publications

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“…Lymphangiogenesis, the formation of new lymphatic vessels, is also thought to be crucial for cancer cells to metastasize to the regional lymph nodes in many cancers, including HNSCC . Therefore, targeting angiogenesis and/or lymphangiogenesis is considered promising for cancer therapy, and many inhibitors have already been approved by the US Food and Drug Administration (FDA) …”

Section: Introductionmentioning

confidence: 99%

Lymphotoxin‐α promotes tumor angiogenesis in HNSCC by modulating glycolysis in a PFKFB3‐dependent manner

Yang

Wang

Xia

et al. 2019

Intl Journal of Cancer

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Tumor angiogenesis is critical for tumor progression as the new blood vessels supply nutrients and facilitate metastasis. Previous studies indicate tumor associated lymphocytes, including B cells and T cells, contribute to tumor angiogenesis and tumor progression. The present study aims to identify the function of Lymphotoxin‐α (LT‐α), which is secreted by the activated lymphocytes, in the tumor angiogenesis of head and neck squamous cell carcinoma (HNSCC). The coculture system between HNSCC cell line Cal27 and primary lymphocytes revealed that tumor cells promoted the LT‐α secretion in the cocultured lymphocytes. In vitro data further demonstrated that LT‐α promoted the proliferation, migration and tube formation of human umbilical vein endothelial cells (HUVECs) by enhancing the PFKFB3‐mediated glycolytic flux. Genetic and pharmacological inhibition of PFKFB3 suppressed the enhanced proliferation and migration of HUVECs. We further identified that LT‐α induced PFKFB3 expression was dependent on the TNFR/NF‐κB signaling pathway. In addition, we proved that PFKFB3 blockade decreased the density of CD31 positive blood vessels in HNSCC xenografts. Finally, the results from the human HNSCC tissue array revealed that the expression of LT‐α in HNSCC samples positively correlated with microvessel density, lymphocytes infiltration and endothelial PFKFB3 expression. In conclusion, infiltrated lymphocyte secreted LT‐α enhances the glycolysis of ECs in a PFKFB3‐dependent manner through the classical NF‐κB pathway and promotes the proliferation and migration of ECs, which may contribute to the aberrant angiogenesis in HNSCCs. Our study suggests that PFKFB3 blockade is a promising therapeutic approach for HNSCCs by targeting tumor angiogenesis.

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Section: Introductionmentioning

confidence: 99%

Lymphotoxin‐α promotes tumor angiogenesis in HNSCC by modulating glycolysis in a PFKFB3‐dependent manner

Yang

Wang

Xia

et al. 2019

Intl Journal of Cancer

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“…Anti‐angiogenic drugs prevent the formation of new blood vessels, whereas anti‐vascular therapy is targeted at the existing tumour vasculature …”

Section: Control Of Angiogenesismentioning

confidence: 99%

“…Abnormal activation of specific TKs has been demonstrated in many neoplasms, making them attractive molecular targets for anticancer therapy. These drugs include semaxanib, vandetanib, cediranib, sorafenib, masitinib, toceranib and sunitinib …”

Section: Control Of Angiogenesismentioning

confidence: 99%

“…They rapidly disrupt the microvascular endothelial lining, resulting in thrombosis and ischaemic–hypoxic tumour necrosis, which is much more pronounced in central than peripheral regions of the tumour. However, anti‐VEGF agents are not effective against mature blood vessels, which seem to lose their dependence on this pro‐angiogenic factor …”

Section: Control Of Angiogenesismentioning

confidence: 99%

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Tumour angiogenesis, anti‐angiogenic therapy and chemotherapeutic resistance

Mander

Finnie

2018

Aust Veterinary J

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In order for a tumour to continue to grow and disseminate, it must acquire a new blood supply. Neovascularisation can be enacted by a number of different mechanisms. This dependence of tumour progression on an augmented vascular supply has been exploited by the development of anti‐angiogenic drugs, which are designed to inhibit new blood vessel formation or disrupt existing tumour‐associated vasculature, both leading to ischaemic–hypoxic tumour cell death. However, the clinical benefits of these therapeutic approaches are frequently variable and often transient, the neoplasm sometimes being able to use other neovascularisation mechanisms to maintain its blood supply and thus evade the current anti‐angiogenic therapy. Tumours may also develop a more malignant phenotype following this treatment. Clinical outcomes may be improved by simultaneously inhibiting different angiogenic pathways, abetted by more effective drug delivery regimens such as metronomic chemotherapy and the concurrent use of other antitumour modalities.

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“…In 2004, the US Food and Drug Administration (FDA) approved a first‐in‐class anti‐VEGF monoclonal antibody (mAb), bevacizumab (brand name Avastin) , for the treatment of metastatic carcinoma of the colon and rectum, and later approved the drug for other indications including nonsmall cell lung cancer and other cancers (Figure ). Bevacizumab acts by binding to VEGF‐A preventing it from activating VEGF receptor 2 (VEGFR2), which is a key player in the pro‐angiogenic pathway . Aflibercept , sorafenib , sunitinib , axitinib , nintedanib , regorafenib , pazobanib , cabozantinib , vandetanib , and thalidomide are among the 26 antiangiogenic agents that are now approved for the treatment of various cancers (Table ).…”

Section: Introductionmentioning

confidence: 99%

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

Yamakawa

Doh

Santosa

et al. 2018

Medicinal Research Reviews

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In recent years, lymphangiogenesis, the process of lymphatic vessel formation from existing lymph vessels, has been demonstrated to have a significant role in diverse pathologies, including cancer metastasis, organ graft rejection, and lymphedema. Our understanding of the mechanisms of lymphangiogenesis has advanced on the heels of studies demonstrating vascular endothelial growth factor C as a central pro-lymphangiogenic regulator and others identifying multiple lymphatic endothelial biomarkers. Despite these breakthroughs and a growing appreciation of the signaling events that govern the lymphangiogenic process, there are no FDA-approved drugs that target lymphangiogenesis. In this review, we reflect on the lessons available from the development of antiangiogenic therapies (26 FDA-approved drugs to date), review current lymphangiogenesis research including nanotechnology in therapeutic drug delivery and imaging, and discuss molecules in the lymphangiogenic pathway that are promising therapeutic targets.

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Anti-angiogenic agents for the treatment of solid tumors: Potential pathways, therapy and current strategies – A review

Abstract: Graphical abstract

Cited by 157 publications

References 195 publications

Lymphotoxin‐α promotes tumor angiogenesis in HNSCC by modulating glycolysis in a PFKFB3‐dependent manner

Lymphotoxin‐α promotes tumor angiogenesis in HNSCC by modulating glycolysis in a PFKFB3‐dependent manner

Tumour angiogenesis, anti‐angiogenic therapy and chemotherapeutic resistance

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

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