Antiangiogenic therapy: a universal chemosensitization strategy for cancer?
For more than 50 years, a major goal of research in cancer therapeutics has been to develop universally effective agents that render cancer cells more sensitive to cytotoxic chemotherapy without substantially increasing toxicity to normal cells. The results of recent clinical trials indicate that certain antiangiogenic drugs may produce this long-sought effect. Here, I describe three distinct mechanisms that may help to explain the chemosensitizing activity of these drugs: normalizing tumor vasculature, preventing rapid tumor cell repopulation, and augmenting the antivascular effects of chemotherapy. I then discuss how these potential mechanisms might be exploited to maximize therapeutic efficacy.
Kerbel
Robert S
RS
Sunnybrook Health Sciences Centre, Departments of Medical Biophysics and Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario M4N 3M5, Canada. robert.kerbel@sri.utoronto.ca
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D049109:Cell Proliferation; D002986:Clinical Trials as Topic; D004334:Drug Administration Schedule; D006801:Humans; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy
D020533:Angiogenesis Inhibitors