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Profile of trebananib (AMG386) and its potential in the treatment of ovarian cancer.

Liontos M, Lykka M, Dimopoulos MA, Bamias A - Onco Targets Ther (2014)

Bottom Line: However, resistance eventually develops and treatment with bevacizumab is associated with increased risk for toxicities such as thromboembolic and hemorrhagic events, gastrointestinal perforation, and impaired wound healing, suggesting the need for new therapeutic approaches.Targeting of the angiopoietins/Tie2 pathway has gained accumulating interest during the last few years as a strategy to overcome bevacizumab resistance and toxicities.Trebananib is a first-in-class peptibody that inhibits angiopoietin 1 and 2 interaction with their receptor Tie2.

View Article: PubMed Central - PubMed

Affiliation: Oncology Department, Therapeutics Clinic, Medical School, University of Athens, Athens, Greece.

ABSTRACT
Angiogenesis has been implicated in ovarian cancer pathogenesis. Bevacizumab, an anti-vascular endothelial growth factor monoclonal antibody, has recently been incorporated in ovarian cancer treatment in combination with chemotherapy both in a frontline setting and in disease recurrence. However, resistance eventually develops and treatment with bevacizumab is associated with increased risk for toxicities such as thromboembolic and hemorrhagic events, gastrointestinal perforation, and impaired wound healing, suggesting the need for new therapeutic approaches. Targeting of the angiopoietins/Tie2 pathway has gained accumulating interest during the last few years as a strategy to overcome bevacizumab resistance and toxicities. Trebananib is a first-in-class peptibody that inhibits angiopoietin 1 and 2 interaction with their receptor Tie2. The molecular profile of this agent, the preclinical data, and clinical studies demonstrating its efficacy in ovarian cancer are discussed in this review.

No MeSH data available.


Related in: MedlinePlus

Angiopoietin (Ang)/Tie2 pathway and its role in vascular remodeling. Ang1 binding to the Tie2 receptor activates prosurvival pathways, decreases endothelial cell permeability, and stabilizes vessels by recruiting pericytes. Ang2 acts antagonistically to the Ang1/Tie2 binding, promoting sprouting angiogenesis through facilitating vascular endothelial growth factor-dependent proangiogenic pathways.
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f1-ott-7-1837: Angiopoietin (Ang)/Tie2 pathway and its role in vascular remodeling. Ang1 binding to the Tie2 receptor activates prosurvival pathways, decreases endothelial cell permeability, and stabilizes vessels by recruiting pericytes. Ang2 acts antagonistically to the Ang1/Tie2 binding, promoting sprouting angiogenesis through facilitating vascular endothelial growth factor-dependent proangiogenic pathways.

Mentions: These data denote the need to improve our understanding of the mechanisms of angiogenesis and to develop more efficient and less toxic treatment. Angiogenesis is one of the hallmarks of cancer.14,15 Formation of new vessels is a prerequisite for growing tumors to maintain supply of oxygen and nutrients.16 In solid tumors, six different mechanisms of new vessel formation have been recognized, namely sprouting angiogenesis, intussusceptive angiogenesis, the recruitment of endothelial progenitor cells, vessel cooption, vasculogenic mimicry, and lymphangiogenesis.17 The VEGF pathway is mainly implicated in sprouting angiogenesis. Anti-VEGF treatment blocks this mechanism, but concomitantly enhances alternative pathways of new vessel formation as is vessel cooption, that is driven by the angiopoietin (Ang)/Tie2 pathway (Figure 1).18,19 The latter signifies that novel agents targeting the Ang/Tie pathway could provide clinical benefit. Trebananib is the most clinically advanced inhibitor of this pathway, and its formulation, as well as available preclinical and clinical data focusing mainly on clinical cancer, are herein analyzed.


Profile of trebananib (AMG386) and its potential in the treatment of ovarian cancer.

Liontos M, Lykka M, Dimopoulos MA, Bamias A - Onco Targets Ther (2014)

Angiopoietin (Ang)/Tie2 pathway and its role in vascular remodeling. Ang1 binding to the Tie2 receptor activates prosurvival pathways, decreases endothelial cell permeability, and stabilizes vessels by recruiting pericytes. Ang2 acts antagonistically to the Ang1/Tie2 binding, promoting sprouting angiogenesis through facilitating vascular endothelial growth factor-dependent proangiogenic pathways.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4199819&req=5

f1-ott-7-1837: Angiopoietin (Ang)/Tie2 pathway and its role in vascular remodeling. Ang1 binding to the Tie2 receptor activates prosurvival pathways, decreases endothelial cell permeability, and stabilizes vessels by recruiting pericytes. Ang2 acts antagonistically to the Ang1/Tie2 binding, promoting sprouting angiogenesis through facilitating vascular endothelial growth factor-dependent proangiogenic pathways.
Mentions: These data denote the need to improve our understanding of the mechanisms of angiogenesis and to develop more efficient and less toxic treatment. Angiogenesis is one of the hallmarks of cancer.14,15 Formation of new vessels is a prerequisite for growing tumors to maintain supply of oxygen and nutrients.16 In solid tumors, six different mechanisms of new vessel formation have been recognized, namely sprouting angiogenesis, intussusceptive angiogenesis, the recruitment of endothelial progenitor cells, vessel cooption, vasculogenic mimicry, and lymphangiogenesis.17 The VEGF pathway is mainly implicated in sprouting angiogenesis. Anti-VEGF treatment blocks this mechanism, but concomitantly enhances alternative pathways of new vessel formation as is vessel cooption, that is driven by the angiopoietin (Ang)/Tie2 pathway (Figure 1).18,19 The latter signifies that novel agents targeting the Ang/Tie pathway could provide clinical benefit. Trebananib is the most clinically advanced inhibitor of this pathway, and its formulation, as well as available preclinical and clinical data focusing mainly on clinical cancer, are herein analyzed.

Bottom Line: However, resistance eventually develops and treatment with bevacizumab is associated with increased risk for toxicities such as thromboembolic and hemorrhagic events, gastrointestinal perforation, and impaired wound healing, suggesting the need for new therapeutic approaches.Targeting of the angiopoietins/Tie2 pathway has gained accumulating interest during the last few years as a strategy to overcome bevacizumab resistance and toxicities.Trebananib is a first-in-class peptibody that inhibits angiopoietin 1 and 2 interaction with their receptor Tie2.

View Article: PubMed Central - PubMed

Affiliation: Oncology Department, Therapeutics Clinic, Medical School, University of Athens, Athens, Greece.

ABSTRACT
Angiogenesis has been implicated in ovarian cancer pathogenesis. Bevacizumab, an anti-vascular endothelial growth factor monoclonal antibody, has recently been incorporated in ovarian cancer treatment in combination with chemotherapy both in a frontline setting and in disease recurrence. However, resistance eventually develops and treatment with bevacizumab is associated with increased risk for toxicities such as thromboembolic and hemorrhagic events, gastrointestinal perforation, and impaired wound healing, suggesting the need for new therapeutic approaches. Targeting of the angiopoietins/Tie2 pathway has gained accumulating interest during the last few years as a strategy to overcome bevacizumab resistance and toxicities. Trebananib is a first-in-class peptibody that inhibits angiopoietin 1 and 2 interaction with their receptor Tie2. The molecular profile of this agent, the preclinical data, and clinical studies demonstrating its efficacy in ovarian cancer are discussed in this review.

No MeSH data available.


Related in: MedlinePlus