A review and update of the current status of the vasculature-disabling agent combretastatin-A4 phosphate (CA4P).
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.
Siemann
Dietmar W
DW
Department of Radiation Oncology, University of Florida, 2000 SW Archer Road, Gainesville, FL 32610, USA. siemadw@ufl.edu
Chaplin
David J
DJ
Walicke
Patricia A
PA
D020533:Angiogenesis Inhibitors / Q000032:analysis / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy*; D013267:Stilbenes / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*
D020533:Angiogenesis Inhibitors; D000972:Antineoplastic Agents, Phytogenic; D013267:Stilbenes; C058728:fosbretabulin