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STA-9584
Vascular Disrupting Agent
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Program Overview
Vascular disrupting agents (VDAs) are a relatively new group of vascular
targeting agents that exhibit selective activity against established tumor
vascular networks, causing severe interruption of tumor blood flow and necrosis
of the tumor mass.1
The first generation of therapeutic vascular targeting agents focused on the use
of anti-angiogenic approaches, which prevent the neovascularization process
and/or promote vascular normalization (thus enhancing chemotherapy) in tumors.2
These drugs have been clinically and commercially successful, and include the
monoclonal antibody bevacizumab (Avastin) and the small molecule kinase
inhibitors sorafenib (Nexavar) and sunitinib (Sutent).
About STA-9584
STA-9584 is a novel, injectable, small molecule compound designed to rapidly
destroy new and established tumor vasculature. Tests in tumor models have
demonstrated the robust, rapid efficacy of STA-9584 against both
chemotherapy-sensitive and -resistant tumors, as well as a promising safety
profile. First generation angiogenesis inhibitors, such as Avastin, work
primarily by preventing the formation of new tumor vessels. We believe that
STA-9584's more complete anti-vasculature mechanism, in combination with an
independent ability to directly kill cancer cells, may increase the potential
anti-cancer activity of this compound versus first generation angiogenesis
inhibitors and other endothelial cell-targeted agents.
Mechanism of Action
The mechanism of action of this class is summarized in the following
figure[Adapted from Tozer et al.3]. VDAs inhibit tumor blood flow by
preferentially targeting the endothelial cell lining of tumor microvasculature,
resulting in decrease blood flow, tumor hypoxia and the rapid onset within
hours of central tumor necrosis.
In preclinical models, it was demonstrated that STA-9584 efficiently kills both
cancer cells in tumors, as well as the endothelial cells that form blood
vessels in tumors, without affecting the vasculature of non-tumor tissues.
Because STA-9584 appears to be highly potent and possesses a mechanism that is
different from many other classes of anti-cancer agents, we believe that
STA-9584 has the potential to be used in both single-agent and combination
settings in the clinic.
Click here for further review
of VDA.
STA-9584 Development Plans
Under the Department of Defense Prostate Cancer Research Program (PCRP) of the
Office of the Congressionally Directed Medical Research Programs (CDMRP),
STA-9584 was approved for a grant of approximately $1 million. This funding
supports the study of STA-9584 in advanced prostate cancer. Synta expects to
complete studies supported by this grant in the first half of 2012.
Presentations
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Title |
Link |
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100th AACR Annual Meeting
April 12-16, 2008 - San Diego, CA
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Vascular Disrupting Agent STA-9584 Selectively Targets
Microvasculature at Both the Center and Periphery of Tumors.
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Poster
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Joint Molecular Imaging Conference
September 8-11, 2007 - Providence, RI |
The Vascular Disrupting Agent STA-9584 Reduces Tumor
Blood Flow in Both Evan’s Blue Dye and Fluorescence Molecular Tomography
Assays.
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Poster
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References for Vascular Disrupting
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Kanthou C and Tozer GM. Microtubule depolymerizing vascular disrupting agents:
novel therapeutics for oncology and other pathologies. Int J Exp Pathol. 2009;
90:284-294.
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Grothley A and Galanis E. Targeting angiogenesis: progress with anti-VEGF
treatment with large molecules. Nat Rev Clin Oncol. 2009; 6:507-518.
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Tozer GM, Kanthou C, Baguley BC. Disrupting tumour blood vessels. Nat Rev Cancer
2005; 5:423-435.
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Thorpe PE. Vascular targeting agents as cancer therapeutics. Clin Cancer Res.
2004 Jan 15;10(2):415-27.
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