Antiangiogenesis beyond VEGF inhibition: A journey from antiangiogenic single-target to broad-spectrum agents

Limaverde-Sousa, Gabriel; Sternberg, Cinthya; Ferreira, Carlos Gil

doi:10.1016/j.ctrv.2013.11.009

Cited by 69 publications

(59 citation statements)

References 98 publications

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“…Endostatin, one of the most potent anti-angiogenic factors, was first isolated in Folkman's lab in 1997, and was reported to dramatically shrink tumor blood formation in mice [2], and interfere with multiple key angiogenesis processes. Pre-clinical studies showed that endostatin also inhibited tumor cell growth [3][4][5], but its insoluble and unstable nature coupled with the high cost of synthesizing the endostatin protein doomed it for clinical use. Intrigued by Folkman's pioneering discoveries, Chinese scientists found a way to refold the protein, making it cost-effective to manufacture a soluble and stable form of endostatin.…”

Section: Introductionmentioning

confidence: 99%

Current Status and Study Progress of Recombinant Human Endostatin in Cancer Treatment

Shi

Qin

2018

Oncol Ther

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Angiogenesis plays fundamentally critical roles in solid-tumor pathogenesis, growth, invasion and metastasis. Endostatin, one of the most potent anti-angiogenic factors, was first isolated in Folkman's lab in 1997, and was reported to dramatically shrink tumor blood formation. But its insoluble and unstable nature coupled with the high cost of synthesizing the endostatin protein doomed it for clinical cancer treatment. Intrigued by Folkman's pioneering discoveries, Chinese scientists found a way to refold the protein, making it cost-effective to manufacture a recombinant human endostatin, a soluble and stable form of endostatin. A number of clinical studies have demonstrated the significant survival benefit of rh-endostatin in treating late stage non-small-cell lung carcinoma (NSCLC) and, as a result, rh-endostatin (Endostar Ò ) was approved by the State Food and Drug Administration of China (CFDA) in September of 2005 as a treatment option for NSCLC. Since then, increasing bodies of clinical data and experience have been obtained from a variety of other different cancers, such as small cell lung cancer, NSCLC in other settings, including malignant serous effusion, melanoma, colon cancer, gastric cancer, breast cancer, nasopharyngeal cancers, and others. This review aims at summarizing current clinical data of rh-endostatin including its survival benefits, optimized dosages, routes of administration, recommended duration and frequency of treatment, predictive biomarkers, and its safety profile in lung cancers as well as other cancers.

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Section: Introductionmentioning

confidence: 99%

Current Status and Study Progress of Recombinant Human Endostatin in Cancer Treatment

Shi

Qin

2018

Oncol Ther

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“…When combined with chemotherapy, synergistic effects have been reported (10,11). However, clinical trials of breast cancer patients with the anti-VEGF antibody bevacizumab, also in combination with chemotherapy have shown variable results and no clear clinical improvement yet (12).…”

Section: Introductionmentioning

confidence: 99%

Activin Receptor-like Kinase 1 Ligand Trap Reduces Microvascular Density and Improves Chemotherapy Efficiency to Various Solid Tumors

Hawinkels

Vinuesa

Paauwe

et al. 2016

Clinical Cancer Research

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Purpose: Antiangiogenic therapy, mostly targeting VEGF, has been applied in cancer patients for the last decade. However, resistance to anti-VEGF therapy and/or no significant benefit as monotherapeutic agent is often observed. Therefore, new antiangiogenic strategies are needed. In the current study, we investigated the therapeutic effect of interfering with the bone morphogenetic protein (BMP)9/activin receptor-like kinase (ALK)1 signaling pathway by using an ALK1-Fc ligand trap.Experimental Design: We analyzed the potential antiangiogenic and antitumor effects of ALK1-Fc protein as monotherapy and in combination with chemotherapy in vivo in mouse models of melanoma, head and neck cancer, and invasive lobular breast carcinomas. ALK1-Fc sequesters BMP9 and 10 and prevents binding of these ligands to endothelial ALK1, which regulates angiogenesis.Results: Treatment of mice with ALK1-Fc strongly decreased the tumors' microvascular density in the three different mouse cancer models. However, this effect was not accompanied by a reduction in tumor volume. An immunohistochemical analysis of the tumor samples revealed that ALK1-Fc treatment increased the pericyte coverage of the remaining tumor vessels and decreased the hypoxia within the tumor. Next, we observed that combining ALK1-Fc with cisplatin inhibited tumor growth in the breast and head and neck cancer models more efficiently than chemotherapy alone.Conclusions: The addition of ALK1-Fc to the cisplatin treatment was able to enhance the cytotoxic effect of the chemotherapy. Our results provide strong rationale to explore combined targeting of ALK1 with chemotherapy in a clinical setting, especially in the ongoing phase II clinical trials with ALK1-Fc.

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“…[12] Eg: ABT510. Antiangiogenic agents alone like cetuximab and ABT 510 have gained approval for use for the treatment of head and neck cancers.…”

Section: Antiangiogenic Agentsmentioning

confidence: 99%

“…Antiangiogenic agents alone like cetuximab and ABT 510 have gained approval for use for the treatment of head and neck cancers. [12] RT being the conventional treatment for HNSCC makes it imperative in this present era to recognize the communication between antiangiogenic therapy and RT, thus developing a combination therapy to achieve progress in the outcome of clinical practice.…”

Section: Antiangiogenic Agentsmentioning

confidence: 99%

Vascular normalization window: A positive prognostic foresight for head and neck cancer

Asha¹,

Dua²,

Rajarathnam³

et al. 2015

JCRI

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Tumor angiogenesis is a hallmark of advanced cancers which is critical for the continued growth and progression of solid tumors owing to the metastatic spread of tumor cells. This knowledge has led to the concept of targeting the tumor vasculature as a therapeutic modality. Several retrospective studies support the positive prognosis for the implications of angiogenic markers for head and neck squamous cell carcinoma (HNSCC), currently making them an attractive target oriented treatment. Radiotherapy (RT) being the conventional treatment for HNSCC, makes it imperative in this present era to recognize the communication between antiangiogenic therapy and RT, thus developing a combination therapy to achieve progress in the outcome of clinical practice. The combination of antiangiogenic agents and ionizing radiation involve many interactions between the cells, the stroma of the tumor and tissue vasculature. Increased angiogenesis is responsible for the proliferation of tumor cells and its metastasis which ultimately leads to tumor hypoxia. Any agent targeting the tumor vasculature can modulate the tumor microenvironment thus normalizing it and enhancing the therapeutic response of hypoxic cells of head and neck cancers. This review provides insight into the mechanisms by which the antiangiogenic therapy combined with RT improves the tumor response to radiation, thereby suggesting a promising prognostic treatment modality of HNSCC in the time ahead.

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Antiangiogenesis beyond VEGF inhibition: A journey from antiangiogenic single-target to broad-spectrum agents

Cited by 69 publications

References 98 publications

Current Status and Study Progress of Recombinant Human Endostatin in Cancer Treatment

Current Status and Study Progress of Recombinant Human Endostatin in Cancer Treatment

Activin Receptor-like Kinase 1 Ligand Trap Reduces Microvascular Density and Improves Chemotherapy Efficiency to Various Solid Tumors

Vascular normalization window: A positive prognostic foresight for head and neck cancer

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