Journal
EXPERT OPINION ON INVESTIGATIONAL DRUGS
Volume 18, Issue 2, Pages 189-197Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1517/13543780802691068
Keywords
antiangiogenic therapy; CA4P; tubulin depolymerization; vascular-disrupting agents
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Funding
- NCI NIH HHS [R01 CA084408] Funding Source: Medline
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Vascular-disrupting strategies impair a tumor's blood vessel network, which is essential for tumor progression and metastasis. Vascular-disrupting agents (VDAs) cause a rapid and selective vascular shutdown in tumors to produce extensive secondary neoplastic cell death due to ischemia. A lead agent in this therapeutic strategy is the tubulin depolymerizing agent combretastatin-A4 phosphate (CA4P). Used alone, CA4P induces extensive necrosis in a wide variety of preclinical cancer models and significant blood flow reductions in the patient tumors. Preclinical and clinical data further indicate that CA4P can effectively be combined with chemotherapy or radiotherapy. Finally, the potential of combining VDAs with antiangiogenic therapies has shown considerable promise in preclinical models and such combinations are now beginning to be evaluated in patients.
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