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Ref Type Journal Article
PMID (26751478)
Authors Bothwell KD, Folaron M, Seshadri M
Title Preclinical Activity of the Vascular Disrupting Agent OXi4503 against Head and Neck Cancer.
Journal Vol Issue Date Pages Journal Short Title
Cancers 8 1 2016 Cancers (Basel)
URL
Abstract Text Vascular disrupting agents (VDAs) represent a relatively distinct class of agents that target established blood vessels in tumors. In this study, we examined the preclinical activity of the second-generation VDA OXi4503 against human head and neck squamous cell carcinoma (HNSCC). Studies were performed in subcutaneous and orthotopic FaDu-luc HNSCC xenografts established in immunodeficient mice. In the subcutaneous model, bioluminescence imaging (BLI) along with tumor growth measurements was performed to assess tumor response to therapy. In mice bearing orthotopic tumors, a dual modality imaging approach based on BLI and magnetic resonance imaging (MRI) was utilized. Correlative histologic assessment of tumors was performed to validate imaging data. Dynamic BLI revealed a marked reduction in radiance within a few hours of OXi4503 administration compared to baseline levels. However, this reduction was transient with vascular recovery observed at 24 h post treatment. A single injection of OXi4503 (40 mg/kg) resulted in a significant (p < 0.01) tumor growth inhibition of subcutaneous FaDu-luc xenografts. MRI revealed a significant reduction (p < 0.05) in volume of orthotopic tumors at 10 days post two doses of OXi4503 treatment. Corresponding histologic (H&amp;E) sections of Oxi4503 treated tumors showed extensive areas of necrosis and hemorrhaging compared to untreated controls. To the best of our knowledge, this is the first report, on the activity of Oxi4503 against HNSCC. These results demonstrate the potential of tumor-VDAs in head and neck cancer. Further examination of the antivascular and antitumor activity of Oxi4503 against HNSCC alone and in combination with chemotherapy and radiation is warranted.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Combretastatin A1 Diphosphate Combretastatin A1 Diphosphate 0 1
Drug Name Trade Name Synonyms Drug Classes Drug Description
Combretastatin A1 Diphosphate OXi4503|OXi-4503|CA1P Combretastatin A1 Diphosphate (OXi4503) is a vascular disrupting agent that causes microtubule instability, resulting in blood vessel collapse and decreased tumor growth (PMID: 20974154, PMID: 26751478, PMID: 32236943).
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References