The Complexity of Translating Anti-angiogenesis Therapy from Basic Science to the Clinic

Ye, Weilan

doi:10.1016/j.devcel.2016.03.015

Cited by 109 publications

(77 citation statements)

References 122 publications

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“…Immunotherapies including those aimed at clonal neoantigens, as well as neutralizing antibodies and antagonists, will likely offer additional options to inhibit the inflammatory TME and enhance anti-tumor immunity [185–187]. In addition, neutralizing antibodies and antagonists targeting tumor angiogenesis have been tried and are under further evaluation [188–191]. Furthermore, cell type specific targeting may also provide alternative options [192, 193], including TAMs [194, 195], MDSCs [7, 46], and B cells [196].…”

Section: Targeting Opportunitiesmentioning

confidence: 99%

Mechanisms that drive inflammatory tumor microenvironment, tumor heterogeneity, and metastatic progression

Yang

Lin

2017

Seminars in Cancer Biology

128

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Treatment of cancer metastases has been largely ineffective. It is paramount to understand the mechanisms underlying the metastatic process, of which the tumor microenvironment is an indispensable participant. What are the critical cellular and molecular players at the primary tumor site where metastatic cascade initiates? How is tumor-associated inflammation regulated? How do altered vasculatures contribute to metastasis? What is the dynamic nature or heterogeneity of primary tumors and what are the challenges to catch a moving target? This review summarizes recent progress, mechanistic understanding, and options for metastasis-targeted therapy.

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Section: Targeting Opportunitiesmentioning

confidence: 99%

Mechanisms that drive inflammatory tumor microenvironment, tumor heterogeneity, and metastatic progression

Yang

Lin

2017

Seminars in Cancer Biology

128

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“…The advent of therapies that block VEGFA/VEGFR2 signaling, such as TKIs and monoclonal antibodies, and inhibit tumor angiogenesis represents a significant improvement in treatment of certain cancers [203]. Yet, this approach has not met the highest expectation, the complete arrest of tumor growth [206, 225, 226]. A multitude of clinical trials has shown that the benefits of antiangiogenic therapy are limited to an increase in progression-free survival and sometimes overall survival on the order of months [206, 225, 226].…”

Section: Therapeutic Opportunitiesmentioning

confidence: 99%

“…Yet, this approach has not met the highest expectation, the complete arrest of tumor growth [206, 225, 226]. A multitude of clinical trials has shown that the benefits of antiangiogenic therapy are limited to an increase in progression-free survival and sometimes overall survival on the order of months [206, 225, 226]. Moreover, certain cancer types completely fail to respond to antiangiogenic therapy [203, 226].…”

Section: Therapeutic Opportunitiesmentioning

confidence: 99%

Modulation of VEGF receptor 2 signaling by protein phosphatases

Corti

Simons

2017

Pharmacological Research

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Phosphorylation of serines, threonines, and tyrosines is a central event in signal transduction cascades in eukaryotic cells. The phosphorylation state of any particular protein reflects a balance of activity between kinases and phosphatases. Kinase biology has been exhaustively studied and is reasonably well understood, however, much less is known about phosphatases. A large body of evidence now shows that protein phosphatases do not behave as indiscriminate signal terminators, but can function both as negative or positive regulators of specific signaling pathways. Genetic models have also shown that different protein phosphatases play precise biological roles in health and disease. Finally, genome sequencing has unveiled the existence of many protein phosphatases and associated regulatory subunits comparable in number to kinases. A wide variety of roles for protein phosphatase roles have been recently described in the context of cancer, diabetes, hereditary disorders and other diseases. In particular, there have been several recent advances in our understanding of phosphatases involved in regulation of vascular endothelial growth factor receptor 2 (VEGFR2) signaling. The receptor is the principal signaling molecule mediating a wide spectrum of VEGF signal and, thus, is of paramount significance in a wide variety of diseases ranging from cancer to cardiovascular to ophthalmic. This review focuses on the current knowledge about protein phosphatases' regulation of VEGFR2 signaling and how these enzymes can modulate affect its biological effects.

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“…In spite of undoubted beneficial effects in several human neoplasms, however, it is fair to say that in most cases antiangiogenic therapy did not meet the expectations. Drugs interfering with VEGF function, for example, when used in combination with chemotherapy do increase progression-free and, to a lesser extent overall survival [17,18,19]. However, in the vast majority of clinical trials the survival benefit was quite modest and transient.…”

Section: Antiangiogenic Therapymentioning

confidence: 99%

The Pleiotropic Role of L1CAM in Tumor Vasculature

Angiolini

Cavallaro

2017

IJMS

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Angiogenesis, the formation of new vessels, is a key step in the development, invasion, and dissemination of solid tumors and, therefore, represents a viable target in the context of antitumor therapy. Indeed, antiangiogenic approaches have given promising results in preclinical models and entered the clinical practice. However, in patients, the results obtained so far with antiangiogenic drugs have not completely fulfilled expectations, especially because their effect has been transient with tumors developing resistance and evasion mechanisms. A better understanding of the mechanisms that underlie tumor vascularization and the functional regulation of cancer vessels is a prerequisite for the development of novel and alternative antiangiogenic treatments. The L1 cell adhesion molecule (L1CAM), a cell surface glycoprotein previously implicated in the development and plasticity of the nervous system, is aberrantly expressed in the vasculature of various cancer types. L1CAM plays multiple pro-angiogenic roles in the endothelial cells of tumor-associated vessels, thus emerging as a potential therapeutic target. In addition, L1CAM prevents the maturation of cancer vasculature and its inhibition promotes vessel normalization, a process that is thought to improve the therapeutic response of tumors to cytotoxic drugs. We here provide an overview on tumor angiogenesis and antiangiogenic therapies and summarize the current knowledge on the biological role of L1CAM in cancer vasculature. Finally, we highlight the clinical implications of targeting L1CAM as a novel antiangiogenic and vessel-normalizing approach.

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The Complexity of Translating Anti-angiogenesis Therapy from Basic Science to the Clinic

Cited by 109 publications

References 122 publications

Mechanisms that drive inflammatory tumor microenvironment, tumor heterogeneity, and metastatic progression

Mechanisms that drive inflammatory tumor microenvironment, tumor heterogeneity, and metastatic progression

Modulation of VEGF receptor 2 signaling by protein phosphatases

The Pleiotropic Role of L1CAM in Tumor Vasculature

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